rs769883857
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_000337.6(SGCD):c.194A>G(p.Asp65Gly) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000208 in 1,440,428 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. D65D) has been classified as Likely benign.
Frequency
Consequence
NM_000337.6 missense, splice_region
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 |
---|---|---|---|---|---|---|---|
SGCD | NM_000337.6 | c.194A>G | p.Asp65Gly | missense_variant, splice_region_variant | 4/9 | ENST00000337851.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SGCD | ENST00000337851.9 | c.194A>G | p.Asp65Gly | missense_variant, splice_region_variant | 4/9 | 1 | NM_000337.6 | P4 | |
SGCD | ENST00000435422.7 | c.191A>G | p.Asp64Gly | missense_variant, splice_region_variant | 3/8 | 1 | A1 | ||
SGCD | ENST00000517913.5 | c.194A>G | p.Asp65Gly | missense_variant, splice_region_variant | 6/10 | 5 | |||
SGCD | ENST00000524347.2 | c.*58A>G | splice_region_variant, 3_prime_UTR_variant, NMD_transcript_variant | 5/6 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.0000121 AC: 3AN: 247462Hom.: 0 AF XY: 0.00000745 AC XY: 1AN XY: 134174
GnomAD4 exome AF: 0.00000208 AC: 3AN: 1440428Hom.: 0 Cov.: 27 AF XY: 0.00000139 AC XY: 1AN XY: 718032
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Autosomal recessive limb-girdle muscular dystrophy type 2F Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 21, 2022 | This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 65 of the SGCD protein (p.Asp65Gly). This variant is present in population databases (rs769883857, gnomAD 0.01%). 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: 566569). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at