15-29268946-T-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_138704.4(NSMCE3):c.760A>T(p.Thr254Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,614,106 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_138704.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NSMCE3 | NM_138704.4 | c.760A>T | p.Thr254Ser | missense_variant | 1/1 | ENST00000332303.6 | |
ENTREP2 | NM_015307.2 | c.277-16468A>T | intron_variant | ENST00000261275.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NSMCE3 | ENST00000332303.6 | c.760A>T | p.Thr254Ser | missense_variant | 1/1 | NM_138704.4 | P1 | ||
ENTREP2 | ENST00000261275.5 | c.277-16468A>T | intron_variant | 5 | NM_015307.2 | P1 | |||
ENTREP2 | ENST00000560082.1 | c.-12-16468A>T | intron_variant | 4 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152212Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461894Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 727248
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152212Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74360
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 18, 2023 | This sequence change replaces threonine, which is neutral and polar, with serine, which is neutral and polar, at codon 254 of the NSMCE3 protein (p.Thr254Ser). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with NSMCE3-related conditions. ClinVar contains an entry for this variant (Variation ID: 1384651). 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 NSMCE3 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at