rs755377592
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PM1PM2PP3_StrongPP5_Moderate
The NM_019616.4(F7):c.1219G>A(p.Ala407Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000198 in 1,612,338 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. A407A) has been classified as Uncertain significance.
Frequency
Consequence
NM_019616.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
F7 | NM_019616.4 | c.1219G>A | p.Ala407Thr | missense_variant | 8/8 | ENST00000346342.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
F7 | ENST00000346342.8 | c.1219G>A | p.Ala407Thr | missense_variant | 8/8 | 1 | NM_019616.4 | P2 | |
F7 | ENST00000375581.3 | c.1285G>A | p.Ala429Thr | missense_variant | 9/9 | 1 | A2 | ||
F7 | ENST00000541084.5 | c.1033G>A | p.Ala345Thr | missense_variant | 6/6 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152200Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000765 AC: 19AN: 248338Hom.: 0 AF XY: 0.0000740 AC XY: 10AN XY: 135056
GnomAD4 exome AF: 0.0000205 AC: 30AN: 1460138Hom.: 0 Cov.: 33 AF XY: 0.0000179 AC XY: 13AN XY: 726316
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152200Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74354
ClinVar
Submissions by phenotype
Factor VII deficiency Pathogenic:1
Likely pathogenic, no assertion criteria provided | clinical testing | Baylor Genetics | Jun 30, 2014 | Our laboratory reported dual molecular diagnoses in F7 (NM_000131.4, c.1285G>A) and MECP2 (NM_004992.3, c.332G>A) in this individual with reported features of motor delay, intellectual disability, hypotonia, bilateral sensorineural hearing loss, skeletal abnormalities, hypertrichosis, and factor VII deficiency. The F7 variant has been previously found in patients with Factor VII deficiency (FA7D) [MIM:227500] (PMID 18976247), and is considered likely pathogenic. The patient's mother was similarly affected with factor VII deficiency and was homozygous for the variant. Heterozygotes are expected to be asymptomatic carriers. - |
F7-related disorder Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 26, 2023 | The F7 c.1285G>A variant is predicted to result in the amino acid substitution p.Ala429Thr. This variant (aka p.Ala369Thr) has been reported in individuals with Factor VII deficiency (Herrmann et al 2009. PubMed ID: 18976247; Ravanbod et al. 2022. PubMed ID: 36760778; Pshenichnikova et al. 2023. PubMed ID: 37761907). A different missense substitution at this same codon (c.1286C>T, Ala429Val) has been reported in an individual with factor VII deficiency (Tang et al. 2022. PubMed ID: 35349734) suggesting that substitution of amino acid residue Ala429 is not tolerated. This variant is reported in 0.041% of alleles in individuals of Latino descent in gnomAD. This variant is interpreted as likely pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at