ClinVar Miner

Submissions for variant NM_000044.6(AR):c.1174C>T (p.Pro392Ser)

gnomAD frequency: 0.00163  dbSNP: rs201934623
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 13
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
UCLA Clinical Genomics Center, UCLA RCV000196772 SCV000255325 pathogenic Partial androgen insensitivity syndrome 2014-07-01 criteria provided, single submitter clinical testing
Genetic Services Laboratory, University of Chicago RCV000499525 SCV000593280 benign not specified 2016-09-22 criteria provided, single submitter clinical testing
Mendelics RCV000990850 SCV001141898 benign Androgen resistance syndrome 2024-02-28 criteria provided, single submitter clinical testing
Clinical Genetics and Genomics, Karolinska University Hospital RCV001269900 SCV001450250 pathogenic not provided 2014-08-20 criteria provided, single submitter clinical testing
Invitae RCV001516905 SCV001725277 benign Androgen resistance syndrome; Kennedy disease 2024-01-31 criteria provided, single submitter clinical testing
Pars Genome Lab RCV002221510 SCV002098054 benign Androgen resistance syndrome; Partial androgen insensitivity syndrome 2022-02-21 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV001269900 SCV004165241 benign not provided 2023-07-01 criteria provided, single submitter clinical testing AR: PP3, BS1, BS2
Clinical Biochemistry Laboratory, Health Services Laboratory RCV000990850 SCV004190290 likely benign Androgen resistance syndrome 2023-11-20 criteria provided, single submitter clinical testing ACMG:PM1 PP3 BS1 BP2 BP4
Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics RCV000627669 SCV000746022 uncertain significance Hypospadias 1, X-linked 2018-01-31 no assertion criteria provided clinical testing The observed variant c.1174C>T (p.P392S) has the minor allele frequency of 0.74% in 1000 Genomes and 0.8% in ExAC databases. The in silico predictions of the variant is polymorphism by Mutation Taster, benign by PolyPhen and damaging by SIFT.
Department of Pathology and Laboratory Medicine, Sinai Health System RCV001269900 SCV001549096 likely benign not provided no assertion criteria provided clinical testing The AR p.Pro392Ser variant was identified in 4 of 584 proband chromosomes (frequency: 0.00685) from a Caucasian population presenting with isolated hypospadias without micropenis or cryptorchidism, and was not identified in 690 control chromosomes from healthy individuals (Kalfa_2013_23637914). The variant was also identified in dbSNP (ID: rs201934623) as "With Pathogenic allele" and ClinVar (3 submissions with conflicting interpretations of pathogenicity: Benign(1) by Genetic Services Laboratory, University of Chicago (2016); Pathogenic(1) by UCLA Clinical Genomics Center, UCLA - CES (2014); and Uncertain significance(1) by Foundation for Research in Genetics and Endocrinology, Institute of Human Genetics (2018)). Submitters report the variant to be linked to Partial Androgen Insensitivity syndrome and Hypospadias 1, X-linked. The variant was also identified in Clinvitae, Cosmic, MutDB, and LOVD 3.0 (likely benign). The variant was identified in control databases in 684 of 166808 chromosomes (4 homozygous) at a frequency of 0.004101 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: South Asian in 404 of 16297 chromosomes (freq: 0.02479), Other in 16 of 4579 chromosomes (freq: 0.003494), Ashkenazi Jewish in 22 of 6922 chromosomes (freq: 0.003178), European (non-Finnish) in 189 of 71137 chromosomes (freq: 0.002657), Latino in 46 of 25450 chromosomes (freq: 0.001807), African in 5 of 14750 chromosomes (freq: 0.000339), East Asian in 1 of 12487 chromosomes (freq: 0.00008), and European (Finnish) in 1 of 15186 chromosomes (freq: 0.000066). Chakrabarty et al. identified the variant p.Pro392Ser as a somatic driver mutation in tissue samples of 18 long-standing ulcerative colitis (UC) subjects at high risk of colorectal carcinoma. (Chakrabarty_2017_28524162). The p.Pro392Ser residue is not conserved in mammals and four out of five computational analyses (PolyPhen-2, SIFT, AlignGVGD, and MutationTaster) do not suggest a high likelihood of impact to the protein; however, this information is not predictive enough to rule out pathogenicity. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign. References: Chakrabarty, Sanjiban, et al. "Targeted sequencing-based analyses of candidate gene variants in ulcerative colitis-associated colorectal neoplasia." British journal of cancer 117.1 (2017): 136. Kalfa, Nicolas, et al. "Minor hypospadias: the “tip of the iceberg” of the partial androgen insensitivity syndrome." PloS one 8.4 (2013): e61824.
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) RCV001269900 SCV001799543 likely benign not provided no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV001269900 SCV001972056 likely benign not provided no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV001269900 SCV001978058 likely benign not provided no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.