rs782728089
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 5P and 2B. PM1PM2PP2BP4_Moderate
The NM_006306.4(SMC1A):āc.2792A>Gā(p.Gln931Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000273 in 1,097,441 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
NM_006306.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SMC1A | NM_006306.4 | c.2792A>G | p.Gln931Arg | missense_variant | 18/25 | ENST00000322213.9 | NP_006297.2 | |
SMC1A | NM_001281463.1 | c.2726A>G | p.Gln909Arg | missense_variant | 19/26 | NP_001268392.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SMC1A | ENST00000322213.9 | c.2792A>G | p.Gln931Arg | missense_variant | 18/25 | 1 | NM_006306.4 | ENSP00000323421.3 |
Frequencies
GnomAD3 genomes Cov.: 22
GnomAD3 exomes AF: 0.0000164 AC: 3AN: 183439Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 67889
GnomAD4 exome AF: 0.00000273 AC: 3AN: 1097441Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 362801
GnomAD4 genome Cov.: 22
ClinVar
Submissions by phenotype
Congenital muscular hypertrophy-cerebral syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Oct 07, 2023 | This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 931 of the SMC1A protein (p.Gln931Arg). This variant is present in population databases (rs782728089, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with SMC1A-related conditions. ClinVar contains an entry for this variant (Variation ID: 582909). 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 SMC1A protein function. 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. - |
Congenital muscular hypertrophy-cerebral syndrome;C5393312:Developmental and epileptic encephalopathy, 85, with or without midline brain defects Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Mar 23, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at