rs104894796
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PM1PM2PP3_StrongPP5_Moderate
The NM_004429.5(EFNB1):c.332C>T(p.Thr111Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. T111A) has been classified as Uncertain significance.
Frequency
Consequence
NM_004429.5 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 |
---|---|---|---|---|---|---|---|
EFNB1 | NM_004429.5 | c.332C>T | p.Thr111Ile | missense_variant | 2/5 | ENST00000204961.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EFNB1 | ENST00000204961.5 | c.332C>T | p.Thr111Ile | missense_variant | 2/5 | 1 | NM_004429.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 24
GnomAD4 exome Cov.: 32
GnomAD4 genome ? Cov.: 24
ClinVar
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Sep 04, 2023 | For these reasons, this variant has been classified as Pathogenic. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on EFNB1 function (PMID: 20565770). 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 EFNB1 protein function. This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 111 of the EFNB1 protein (p.Thr111Ile). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with craniofrontonasal syndrome (PMID: 15124102). It has also been observed to segregate with disease in related individuals. This variant is also known as c.1023C>T. ClinVar contains an entry for this variant (Variation ID: 11707). - |
Craniofrontonasal syndrome Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jun 01, 2004 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at