rs561243137
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 6P and 1B. PM1PM2PM5BP4
The ENST00000524377.7(NTRK1):c.1039C>A(p.Arg347Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R347C) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000524377.7 missense
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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NTRK1 | NM_002529.4 | c.1039C>A | p.Arg347Ser | missense_variant | 8/17 | ENST00000524377.7 | NP_002520.2 | |
NTRK1 | NM_001012331.2 | c.1039C>A | p.Arg347Ser | missense_variant | 8/16 | NP_001012331.1 | ||
NTRK1 | NM_001007792.1 | c.949C>A | p.Arg317Ser | missense_variant | 9/17 | NP_001007793.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NTRK1 | ENST00000524377.7 | c.1039C>A | p.Arg347Ser | missense_variant | 8/17 | 1 | NM_002529.4 | ENSP00000431418 | P4 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD4 exome Cov.: 32
GnomAD4 genome Cov.: 31
ClinVar
Submissions by phenotype
Hereditary insensitivity to pain with anhidrosis Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jul 06, 2022 | This sequence change replaces arginine, which is basic and polar, with serine, which is neutral and polar, at codon 347 of the NTRK1 protein (p.Arg347Ser). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. 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 NTRK1 protein function. ClinVar contains an entry for this variant (Variation ID: 1505495). This variant has not been reported in the literature in individuals affected with NTRK1-related conditions. This variant is not present in population databases (gnomAD no frequency). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.