chr13-113106910-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP3PP5_Moderate
The ENST00000375581.3(F7):c.130G>A(p.Val44Ile) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000437 in 1,602,372 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Consequence
ENST00000375581.3 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
F7 | NM_019616.4 | c.64+1005G>A | intron_variant | ENST00000346342.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
F7 | ENST00000375581.3 | c.130G>A | p.Val44Ile | missense_variant, splice_region_variant | 2/9 | 1 | A2 | ||
F7 | ENST00000346342.8 | c.64+1005G>A | intron_variant | 1 | NM_019616.4 | P2 | |||
F7 | ENST00000541084.5 | c.64+1005G>A | intron_variant | 2 | |||||
F7 | ENST00000444337.1 | c.64+1005G>A | intron_variant, NMD_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152046Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000414 AC: 6AN: 1450326Hom.: 0 Cov.: 31 AF XY: 0.00000416 AC XY: 3AN XY: 720428
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 152046Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74262
ClinVar
Submissions by phenotype
Congenital factor VII deficiency Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | May 19, 2023 | Variant summary: F7 c.130G>A (p.Val44Ile) results in a conservative amino acid change located in the Gamma-carboxyglutamic acid-rich (GLA) domain (IPR000294) of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. Several computational tools predict a significant impact on normal splicing: four predict the variant weakens a 5' donor site. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 228846 control chromosomes. c.130G>A has been reported in the literature in at least one homozygous affected with Congenital factor VII deficiency (e.g., Wulff_2000). These data indicate that the variant may be associated with disease. At least one publication reports a homozygous patient to have <10% of normal FVII:C activity (e.g., Wulff_2000). The following publication was ascertained in the context of this evaluation (PMID: 10862079). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at