ClinVar Miner

Submissions for variant NM_000190.4(HMBS):c.1075G>A (p.Asp359Asn)

gnomAD frequency: 0.00039  dbSNP: rs144949995
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000148507 SCV001259472 benign Acute intermittent porphyria 2017-10-13 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.
Labcorp Genetics (formerly Invitae), Labcorp RCV001356682 SCV002447753 likely benign not provided 2025-01-01 criteria provided, single submitter clinical testing
CSER _CC_NCGL, University of Washington RCV000148507 SCV000190218 likely benign Acute intermittent porphyria 2014-06-01 no assertion criteria provided research
Department of Pathology and Laboratory Medicine, Sinai Health System RCV001356682 SCV001551921 uncertain significance not provided no assertion criteria provided clinical testing The HMBS p.Asp302Asn variant was not identified in the literature nor was it identified in Cosmic. The variant was identified in dbSNP (ID: rs144949995), ClinVar (classified as likely benign by the University of Washington Medical Center) and LOVD 3.0. The variant was identified in control databases in 36 of 282466 chromosomes (1 homozygous) at a frequency of 0.000127 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: African in 32 of 24952 chromosomes (freq: 0.001282), Other in 3 of 7224 chromosomes (freq: 0.000415) and European (non-Finnish) in 1 of 128878 chromosomes (freq: 0.000008), while the variant was not observed in the Latino, Ashkenazi Jewish, East Asian, European (Finnish), and South Asian populations. The p.Asp302 residue is not conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.

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