rs121909296
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_000337.6(SGCD):c.89G>A(p.Trp30Ter) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Consequence
SGCD
NM_000337.6 stop_gained
NM_000337.6 stop_gained
Scores
5
1
1
Clinical Significance
Conservation
PhyloP100: 9.86
Genes affected
SGCD (HGNC:10807): (sarcoglycan delta) The protein encoded by this gene is one of the four known components of the sarcoglycan complex, which is a subcomplex of the dystrophin-glycoprotein complex (DGC). DGC forms a link between the F-actin cytoskeleton and the extracellular matrix. This protein is expressed most abundantly in skeletal and cardiac muscle. Mutations in this gene have been associated with autosomal recessive limb-girdle muscular dystrophy and dilated cardiomyopathy. Alternatively spliced transcript variants encoding distinct isoforms have been observed for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 34 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 5-156344574-G-A is Pathogenic according to our data. Variant chr5-156344574-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 8173.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-156344574-G-A is described in Lovd as [Pathogenic]. Variant chr5-156344574-G-A is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SGCD | NM_000337.6 | c.89G>A | p.Trp30Ter | stop_gained | 3/9 | ENST00000337851.9 | |
LOC124901120 | XR_007059016.1 | n.234+2879C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SGCD | ENST00000337851.9 | c.89G>A | p.Trp30Ter | stop_gained | 3/9 | 1 | NM_000337.6 | P4 | |
SGCD | ENST00000435422.7 | c.86G>A | p.Trp29Ter | stop_gained | 2/8 | 1 | A1 | ||
SGCD | ENST00000517913.5 | c.89G>A | p.Trp30Ter | stop_gained | 5/10 | 5 | |||
SGCD | ENST00000524347.2 | c.89G>A | p.Trp30Ter | stop_gained, NMD_transcript_variant | 3/6 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Autosomal recessive limb-girdle muscular dystrophy type 2F Pathogenic:2
Pathogenic, no assertion criteria provided | literature only | OMIM | May 01, 1997 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Nov 27, 2023 | This sequence change creates a premature translational stop signal (p.Trp30*) in the SGCD gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SGCD are known to be pathogenic (PMID: 8841194, 10735275, 10838250). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with clinical features of limb-girdle muscular dystrophy (PMID: 10735275). ClinVar contains an entry for this variant (Variation ID: 8173). For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
MutationTaster
Benign
A;A;A;A
Vest4
GERP RS
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at