NM_000337.6:c.32G>A
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BS1_Supporting
The NM_000337.6(SGCD):c.32G>A(p.Arg11Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000205 in 1,606,788 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_000337.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SGCD | ENST00000337851.9 | c.32G>A | p.Arg11Gln | missense_variant | Exon 3 of 9 | 1 | NM_000337.6 | ENSP00000338343.4 | ||
SGCD | ENST00000435422.7 | c.29G>A | p.Arg10Gln | missense_variant | Exon 2 of 8 | 1 | ENSP00000403003.2 | |||
SGCD | ENST00000517913.5 | c.32G>A | p.Arg11Gln | missense_variant | Exon 5 of 10 | 5 | ENSP00000429378.1 | |||
SGCD | ENST00000524347.2 | n.32G>A | non_coding_transcript_exon_variant | Exon 3 of 6 | 5 | ENSP00000430794.1 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 151876Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000206 AC: 5AN: 243066Hom.: 0 AF XY: 0.0000227 AC XY: 3AN XY: 132074
GnomAD4 exome AF: 0.0000199 AC: 29AN: 1454912Hom.: 0 Cov.: 31 AF XY: 0.0000152 AC XY: 11AN XY: 723484
GnomAD4 genome AF: 0.0000263 AC: 4AN: 151876Hom.: 0 Cov.: 32 AF XY: 0.0000405 AC XY: 3AN XY: 74156
ClinVar
Submissions by phenotype
Autosomal recessive limb-girdle muscular dystrophy type 2F Uncertain:3
This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 11 of the SGCD protein (p.Arg11Gln). This variant is present in population databases (rs752548592, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with SGCD-related conditions. ClinVar contains an entry for this variant (Variation ID: 196256). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. -
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not provided Uncertain:3
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Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 27535533) -
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Autosomal recessive limb-girdle muscular dystrophy type 2F;C1847667:Dilated cardiomyopathy 1L Uncertain:2
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Primary dilated cardiomyopathy Uncertain:1
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Dilated cardiomyopathy 1L Uncertain:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at