rs748926718
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PM1PM2PM5PP3_StrongPP5_Moderate
The NM_000128.4(F11):c.1103G>A(p.Gly368Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000248 in 1,614,024 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 Pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G368A) has been classified as Likely pathogenic.
Frequency
Consequence
NM_000128.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
F11 | NM_000128.4 | c.1103G>A | p.Gly368Glu | missense_variant | 10/15 | ENST00000403665.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
F11 | ENST00000403665.7 | c.1103G>A | p.Gly368Glu | missense_variant | 10/15 | 1 | NM_000128.4 | P1 | |
F11 | ENST00000452239.1 | c.551G>A | p.Gly184Glu | missense_variant | 5/6 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152108Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251366Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135842
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461798Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1AN XY: 727198
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152226Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74424
ClinVar
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Aug 11, 2023 | Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt F11 protein function. Experimental studies have shown that this missense change affects F11 function (PMID: 15026311). This variant disrupts the p.Gly350 amino acid residue in F11. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 14717969). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. This variant is also known as p.Gly350Glu. This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 368 of the F11 protein (p.Gly368Glu). This variant is present in population databases (no rsID available, gnomAD 0.02%). This missense change has been observed in individual(s) with clinical features of autosomal recessive factor XI deficiency (PMID: 33751533). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at