rs199797401
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2
The NM_018834.6(MATR3):c.2234C>T(p.Ala745Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000244 in 1,614,052 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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. A745P) has been classified as Uncertain significance.
Frequency
Consequence
NM_018834.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MATR3 | NM_018834.6 | c.2234C>T | p.Ala745Val | missense_variant | 13/15 | ENST00000394805.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MATR3 | ENST00000394805.8 | c.2234C>T | p.Ala745Val | missense_variant | 13/15 | 1 | NM_018834.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000145 AC: 22AN: 152164Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000795 AC: 20AN: 251464Hom.: 0 AF XY: 0.0000883 AC XY: 12AN XY: 135902
GnomAD4 exome AF: 0.000254 AC: 372AN: 1461888Hom.: 0 Cov.: 33 AF XY: 0.000278 AC XY: 202AN XY: 727246
GnomAD4 genome ? AF: 0.000145 AC: 22AN: 152164Hom.: 0 Cov.: 32 AF XY: 0.000135 AC XY: 10AN XY: 74340
ClinVar
Submissions by phenotype
Amyotrophic lateral sclerosis type 21 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 07, 2023 | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 745 of the MATR3 protein (p.Ala745Val). This variant is present in population databases (rs199797401, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with MATR3-related conditions. ClinVar contains an entry for this variant (Variation ID: 574594). 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 not expected to disrupt MATR3 protein function with a negative predictive value of 80%. 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | May 28, 2019 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at