rs1365539591
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 1P and 8B. PP2BP4_StrongBS2
The NM_015295.3(SMCHD1):c.4894C>G(p.Gln1632Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000106 in 1,601,174 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 (★★).
Frequency
Consequence
NM_015295.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SMCHD1 | NM_015295.3 | c.4894C>G | p.Gln1632Glu | missense_variant | Exon 39 of 48 | ENST00000320876.11 | NP_056110.2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 151900Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000125 AC: 3AN: 239058Hom.: 0 AF XY: 0.0000154 AC XY: 2AN XY: 129730
GnomAD4 exome AF: 0.0000103 AC: 15AN: 1449274Hom.: 0 Cov.: 31 AF XY: 0.0000111 AC XY: 8AN XY: 720326
GnomAD4 genome AF: 0.0000132 AC: 2AN: 151900Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74160
ClinVar
Submissions by phenotype
Facioscapulohumeral muscular dystrophy 2 Uncertain:1
This sequence change replaces glutamine, which is neutral and polar, with glutamic acid, which is acidic and polar, at codon 1632 of the SMCHD1 protein (p.Gln1632Glu). This variant is present in population databases (no rsID available, gnomAD 0.007%). 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: 464168). 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 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. -
not provided Uncertain:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at