ClinVar Miner

Submissions for variant NM_000133.4(F9):c.967G>A (p.Glu323Lys)

gnomAD frequency: 0.00294  dbSNP: rs150351950
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000861890 SCV001002304 benign Hereditary factor IX deficiency disease; Thrombophilia, X-linked, due to factor 9 defect 2025-01-27 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002495223 SCV002810038 likely benign Hereditary factor IX deficiency disease; Thrombophilia, X-linked, due to factor 9 defect; Warfarin sensitivity, X-linked 2022-04-14 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System RCV001358071 SCV001553719 benign not specified no assertion criteria provided clinical testing The F9 p.Glu323Lys variant was identified in 1 male with hemophilia B from a cohort of 3000 individuals (2900 male, 100 female) (frequency: 0.00032258) (Johnsen_ 2017_PMID:29296726). This variant was also reported in 1/3713 individuals with hemophilia B in the Factor IX Gene (F9) Variant Database. The variant was identified in dbSNP (ID: rs150351950), ClinVar (classified as benign by Invitae) and LOVD 3.0.The variant was identified in control databases in 175 of 205225 chromosomes (41 hemizygous) at a frequency of 0.0008527 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database March 6, 2019, v2.1.1). The variant was observed in the following populations: African in 168 of 19054 chromosomes (freq: 0.008817), Latino in 6 of 28025 chromosomes (freq: 0.000214) and East Asian in 1 of 14860 chromosomes (freq: 0.000067), but was not observed in the Ashkenazi Jewish, European (Finnish), European (non-Finnish), Other, and South Asian populations. The p.Glu323 residue is not conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein; however, this information is not predictive enough to rule out 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 this variant meets our laboratory's criteria to be classified as benign.
Natera, Inc. RCV001830862 SCV002082228 likely benign Hereditary factor IX deficiency disease 2019-12-24 no assertion criteria provided clinical testing
PreventionGenetics, part of Exact Sciences RCV003955577 SCV004772286 likely benign F9-related disorder 2022-03-04 no assertion criteria provided clinical testing This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

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