chrX-65716827-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP3_ModerateBS2
The NM_002444.3(MSN):c.22C>T(p.Arg8Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000323 in 1,206,604 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 6 hemizygotes in GnomAD. In-silico tool predicts a pathogenic 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. R8H) has been classified as Likely benign.
Frequency
Consequence
NM_002444.3 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 |
---|---|---|---|---|---|---|---|
MSN | NM_002444.3 | c.22C>T | p.Arg8Cys | missense_variant | 2/13 | ENST00000360270.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MSN | ENST00000360270.7 | c.22C>T | p.Arg8Cys | missense_variant | 2/13 | 1 | NM_002444.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000364 AC: 4AN: 109872Hom.: 0 Cov.: 21 AF XY: 0.00 AC XY: 0AN XY: 32102
GnomAD3 exomes AF: 0.0000109 AC: 2AN: 182834Hom.: 0 AF XY: 0.0000148 AC XY: 1AN XY: 67422
GnomAD4 exome AF: 0.0000319 AC: 35AN: 1096732Hom.: 0 Cov.: 29 AF XY: 0.0000166 AC XY: 6AN XY: 362172
GnomAD4 genome AF: 0.0000364 AC: 4AN: 109872Hom.: 0 Cov.: 21 AF XY: 0.00 AC XY: 0AN XY: 32102
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 11, 2023 | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 8 of the MSN protein (p.Arg8Cys). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with MSN-related conditions. ClinVar contains an entry for this variant (Variation ID: 1486797). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests 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