15-29268817-G-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_138704.4(NSMCE3):c.889C>T(p.Pro297Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000509 in 1,612,070 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 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
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NSMCE3 | NM_138704.4 | c.889C>T | p.Pro297Ser | missense_variant | 1/1 | ENST00000332303.6 | |
ENTREP2 | NM_015307.2 | c.277-16339C>T | intron_variant | ENST00000261275.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NSMCE3 | ENST00000332303.6 | c.889C>T | p.Pro297Ser | missense_variant | 1/1 | NM_138704.4 | P1 | ||
ENTREP2 | ENST00000261275.5 | c.277-16339C>T | intron_variant | 5 | NM_015307.2 | P1 | |||
ENTREP2 | ENST00000560082.1 | c.-12-16339C>T | intron_variant | 4 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152110Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000239 AC: 6AN: 250618Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 135360
GnomAD4 exome AF: 0.0000534 AC: 78AN: 1459960Hom.: 0 Cov.: 31 AF XY: 0.0000510 AC XY: 37AN XY: 725846
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152110Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74308
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Mar 05, 2022 | This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 297 of the NSMCE3 protein (p.Pro297Ser). This variant is present in population databases (rs776476342, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with NSMCE3-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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