rs201131924
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 4P and 3B. PM1PM2BP4_ModerateBP6
The NM_000023.4(SGCA):āc.680C>Gā(p.Pro227Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000219 in 1,614,034 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. P227P) has been classified as Likely benign.
Frequency
Consequence
NM_000023.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SGCA | NM_000023.4 | c.680C>G | p.Pro227Arg | missense_variant | 6/10 | ENST00000262018.8 | |
SGCA | NM_001135697.3 | c.584+615C>G | intron_variant | ||||
SGCA | NR_135553.2 | n.716C>G | non_coding_transcript_exon_variant | 6/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SGCA | ENST00000262018.8 | c.680C>G | p.Pro227Arg | missense_variant | 6/10 | 1 | NM_000023.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000237 AC: 36AN: 152092Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.000298 AC: 75AN: 251360Hom.: 1 AF XY: 0.000346 AC XY: 47AN XY: 135878
GnomAD4 exome AF: 0.000218 AC: 318AN: 1461822Hom.: 0 Cov.: 32 AF XY: 0.000204 AC XY: 148AN XY: 727218
GnomAD4 genome ? AF: 0.000237 AC: 36AN: 152212Hom.: 0 Cov.: 31 AF XY: 0.000309 AC XY: 23AN XY: 74424
ClinVar
Submissions by phenotype
Autosomal recessive limb-girdle muscular dystrophy type 2D Uncertain:3Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Dec 12, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | May 18, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Nov 17, 2019 | - - |
not provided Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Nov 14, 2017 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jan 15, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Apr 01, 2023 | - - |
Sarcoglycanopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at