chr5-156344576-C-T
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_000337.6(SGCD):c.91C>T(p.Arg31Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,609,532 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 Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R31Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_000337.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SGCD | NM_000337.6 | c.91C>T | p.Arg31Trp | missense_variant | 3/9 | ENST00000337851.9 | |
LOC124901120 | XR_007059016.1 | n.234+2877G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SGCD | ENST00000337851.9 | c.91C>T | p.Arg31Trp | missense_variant | 3/9 | 1 | NM_000337.6 | P4 | |
SGCD | ENST00000435422.7 | c.88C>T | p.Arg30Trp | missense_variant | 2/8 | 1 | A1 | ||
SGCD | ENST00000517913.5 | c.91C>T | p.Arg31Trp | missense_variant | 5/10 | 5 | |||
SGCD | ENST00000524347.2 | c.91C>T | p.Arg31Trp | missense_variant, NMD_transcript_variant | 3/6 | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 152036Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000207 AC: 5AN: 241742Hom.: 0 AF XY: 0.0000378 AC XY: 5AN XY: 132314
GnomAD4 exome AF: 0.0000158 AC: 23AN: 1457496Hom.: 0 Cov.: 32 AF XY: 0.0000152 AC XY: 11AN XY: 725020
GnomAD4 genome AF: 0.0000132 AC: 2AN: 152036Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74256
ClinVar
Submissions by phenotype
Autosomal recessive limb-girdle muscular dystrophy type 2F Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Feb 08, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 18, 2022 | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 31 of the SGCD protein (p.Arg31Trp). This variant is present in population databases (rs202223676, 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: 652862). 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. - |
Autosomal recessive limb-girdle muscular dystrophy type 2F;C1847667:Dilated cardiomyopathy 1L Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 18, 2021 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Nov 22, 2021 | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Dilated cardiomyopathy 1L Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Feb 08, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at