rs3093248
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PM1PM2BP4_Strong
The NM_019616.4(F7):c.1267G>A(p.Glu423Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000208 in 1,609,632 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_019616.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
F7 | NM_019616.4 | c.1267G>A | p.Glu423Lys | missense_variant | 8/8 | ENST00000346342.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
F7 | ENST00000346342.8 | c.1267G>A | p.Glu423Lys | missense_variant | 8/8 | 1 | NM_019616.4 | P2 | |
F7 | ENST00000375581.3 | c.1333G>A | p.Glu445Lys | missense_variant | 9/9 | 1 | A2 | ||
F7 | ENST00000541084.5 | c.1081G>A | p.Glu361Lys | missense_variant | 6/6 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00101 AC: 154AN: 152094Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000257 AC: 63AN: 245338Hom.: 0 AF XY: 0.000187 AC XY: 25AN XY: 133720
GnomAD4 exome AF: 0.000124 AC: 180AN: 1457420Hom.: 1 Cov.: 33 AF XY: 0.000102 AC XY: 74AN XY: 725140
GnomAD4 genome ? AF: 0.00101 AC: 154AN: 152212Hom.: 0 Cov.: 33 AF XY: 0.000914 AC XY: 68AN XY: 74398
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Jan 19, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Sep 26, 2023 | Reported in individuals with significantly lower plasma factor VII levels (Huffman et al., 2015); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 34426522, 18976247, 26105150) - |
Congenital factor VII deficiency;C1832662:Myocardial infarction, susceptibility to Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Apr 25, 2022 | - - |
Factor VII deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 28, 2017 | 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. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
F7-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jan 19, 2024 | The F7 c.1333G>A variant is predicted to result in the amino acid substitution p.Glu445Lys. This variant has been reported in cohort studies of Factor VII deficiency (Described as Gly385Lys, Herrmann et al. 2009. PubMed ID: 18976247; Huffman et al. 2015. PubMed ID: 26105150). This variant is reported in 0.33% of alleles in individuals of African descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at