rs903823830
Variant summary
Our verdict is Pathogenic. Variant got 14 ACMG points: 14P and 0B. PM1PM2PP3_ModeratePP5_Very_Strong
The NM_000023.4(SGCA):c.92T>C(p.Leu31Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. L31L) has been classified as Likely benign.
Frequency
Consequence
NM_000023.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 14 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SGCA | NM_000023.4 | c.92T>C | p.Leu31Pro | missense_variant | 2/10 | ENST00000262018.8 | |
SGCA | NM_001135697.3 | c.92T>C | p.Leu31Pro | missense_variant | 2/8 | ||
SGCA | NR_135553.2 | n.128T>C | non_coding_transcript_exon_variant | 2/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SGCA | ENST00000262018.8 | c.92T>C | p.Leu31Pro | missense_variant | 2/10 | 1 | NM_000023.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 0.00000684 AC: 10AN: 1461876Hom.: 0 Cov.: 32 AF XY: 0.00000688 AC XY: 5AN XY: 727244
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Autosomal recessive limb-girdle muscular dystrophy type 2D Pathogenic:6
Pathogenic, criteria provided, single submitter | clinical testing | Undiagnosed Diseases Network, NIH | Jun 30, 2020 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | May 25, 2023 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Feb 14, 2023 | - - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Counsyl | Jan 11, 2017 | - - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Feb 08, 2023 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Oct 03, 2023 | This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 31 of the SGCA protein (p.Leu31Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with autosomal recessive limb-girdle muscular dystrophy (PMID: 9032047, 12566530, 18285821, 29351619). ClinVar contains an entry for this variant (Variation ID: 550333). 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 expected to disrupt SGCA protein function. Experimental studies have shown that this missense change affects SGCA function (PMID: 22095924, 29351619). For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at