rs1057519639
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 5P and 1B. PM1PM2PP2BP4
The NM_015295.3(SMCHD1):c.1034A>G(p.Gln345Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign 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. Q345E) has been classified as Uncertain significance.
Frequency
Consequence
NM_015295.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SMCHD1 | NM_015295.3 | c.1034A>G | p.Gln345Arg | missense_variant | 8/48 | ENST00000320876.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMCHD1 | ENST00000320876.11 | c.1034A>G | p.Gln345Arg | missense_variant | 8/48 | 5 | NM_015295.3 | P2 | |
ENST00000583546.1 | n.371-2807T>C | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Cov.: 30
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Arrhinia with choanal atresia and microphthalmia syndrome Pathogenic:2
Pathogenic, no assertion criteria provided | research | MGH Harvard Center for Reproductive Medicine, Massachusetts General Hospital | - | - - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Feb 27, 2017 | - - |
Anosmia Pathogenic:1
Pathogenic, no assertion criteria provided | research | MGH Harvard Center for Reproductive Medicine, Massachusetts General Hospital | - | - - |
Facioscapulohumeral muscular dystrophy 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 12, 2022 | This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 345 of the SMCHD1 protein (p.Gln345Arg). This variant is not present in population databases (gnomAD no frequency). 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. Experimental studies have shown that this missense change does not substantially affect SMCHD1 function (PMID: 31312724). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 375760). This missense change has been observed in individual(s) with autosomal dominant Bosma arhinia microphthalmia syndrome (PMID: 28067909). It has also been observed to segregate with disease in related individuals. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at