chr18-2724932-A-C
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 1P and 9B. PP2BP4_StrongBS1_SupportingBS2
The NM_015295.3(SMCHD1):āc.2637A>Cā(p.Lys879Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000384 in 1,588,792 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 (ā ā ). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Benign in Lovd.
Frequency
Consequence
NM_015295.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SMCHD1 | NM_015295.3 | c.2637A>C | p.Lys879Asn | missense_variant | 21/48 | ENST00000320876.11 | NP_056110.2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 151896Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000617 AC: 14AN: 226952Hom.: 0 AF XY: 0.0000817 AC XY: 10AN XY: 122364
GnomAD4 exome AF: 0.0000390 AC: 56AN: 1436778Hom.: 0 Cov.: 31 AF XY: 0.0000575 AC XY: 41AN XY: 713346
GnomAD4 genome AF: 0.0000329 AC: 5AN: 152014Hom.: 0 Cov.: 31 AF XY: 0.0000538 AC XY: 4AN XY: 74304
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Sep 09, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Sep 11, 2015 | - - |
Facioscapulohumeral muscular dystrophy 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Nov 19, 2024 | This sequence change replaces lysine, which is basic and polar, with asparagine, which is neutral and polar, at codon 879 of the SMCHD1 protein (p.Lys879Asn). This variant is present in population databases (rs633422, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with SMCHD1-related conditions. ClinVar contains an entry for this variant (Variation ID: 283266). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt SMCHD1 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