rs200166783
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 6P and 2B. PM1PM2PM5BP4_Moderate
The NM_000023.4(SGCA):c.724G>A(p.Val242Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000347 in 1,613,698 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V242F) has been classified as Likely pathogenic.
Frequency
Consequence
NM_000023.4 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 |
---|---|---|---|---|---|---|---|
SGCA | NM_000023.4 | c.724G>A | p.Val242Ile | missense_variant | 6/10 | ENST00000262018.8 | |
SGCA | NM_001135697.3 | c.584+659G>A | intron_variant | ||||
SGCA | NR_135553.2 | n.760G>A | non_coding_transcript_exon_variant | 6/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SGCA | ENST00000262018.8 | c.724G>A | p.Val242Ile | missense_variant | 6/10 | 1 | NM_000023.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152112Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 250958Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135692
GnomAD4 exome AF: 0.0000363 AC: 53AN: 1461586Hom.: 0 Cov.: 32 AF XY: 0.0000330 AC XY: 24AN XY: 727082
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152112Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74290
ClinVar
Submissions by phenotype
Autosomal recessive limb-girdle muscular dystrophy type 2D Uncertain:4
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 09, 2022 | This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 242 of the SGCA protein (p.Val242Ile). This variant is present in population databases (rs200166783, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with SGCA-related conditions. ClinVar contains an entry for this variant (Variation ID: 497383). 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 SGCA protein function. This variant disrupts the p.Val242 amino acid residue in SGCA. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 10842281, 12566530). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. - |
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Mar 09, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Feb 08, 2023 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Nov 30, 2016 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at