5-156595010-A-G
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_000337.6(SGCD):āc.461A>Gā(p.Asn154Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000479 in 1,460,094 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 32)
Exomes š: 0.0000048 ( 0 hom. )
Consequence
SGCD
NM_000337.6 missense
NM_000337.6 missense
Scores
2
15
Clinical Significance
Conservation
PhyloP100: 3.92
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 Uncertain_significance. Variant got 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.16015697).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SGCD | NM_000337.6 | c.461A>G | p.Asn154Ser | missense_variant | 6/9 | ENST00000337851.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SGCD | ENST00000337851.9 | c.461A>G | p.Asn154Ser | missense_variant | 6/9 | 1 | NM_000337.6 | P4 | |
SGCD | ENST00000435422.7 | c.458A>G | p.Asn153Ser | missense_variant | 5/8 | 1 | A1 | ||
SGCD | ENST00000517913.5 | c.461A>G | p.Asn154Ser | missense_variant | 8/10 | 5 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
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32
GnomAD3 exomes AF: 0.00000807 AC: 2AN: 247914Hom.: 0 AF XY: 0.00000744 AC XY: 1AN XY: 134454
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GnomAD4 exome AF: 0.00000479 AC: 7AN: 1460094Hom.: 0 Cov.: 29 AF XY: 0.00000551 AC XY: 4AN XY: 726388
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GnomAD4 genome Cov.: 32
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Autosomal recessive limb-girdle muscular dystrophy type 2F Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 13, 2022 | This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 154 of the SGCD protein (p.Asn154Ser). This variant is present in population databases (rs759767804, gnomAD 0.003%). 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: 532693). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T
M_CAP
Benign
D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
N;N;N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Benign
T;T;T
Sift4G
Benign
T;T;T
Polyphen
B;B;B
Vest4
MutPred
0.37
.;Loss of catalytic residue at N153 (P = 0.0257);.;
MVP
MPC
0.096
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at