rs121909297

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM2PP3_StrongPP5_Moderate

The NM_000337.6(SGCD):​c.784G>A​(p.Glu262Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,320 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 Likely pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. E262E) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SGCD
NM_000337.6 missense

Scores

9
9
1

Clinical Significance

Likely pathogenic criteria provided, single submitter P:2

Conservation

PhyloP100: 9.46
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 8 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.974
PP5
Variant 5-156759301-G-A is Pathogenic according to our data. Variant chr5-156759301-G-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 8174.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-156759301-G-A is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SGCDNM_000337.6 linkuse as main transcriptc.784G>A p.Glu262Lys missense_variant 9/9 ENST00000337851.9 NP_000328.2 Q92629-2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SGCDENST00000337851.9 linkuse as main transcriptc.784G>A p.Glu262Lys missense_variant 9/91 NM_000337.6 ENSP00000338343.4 Q92629-2
SGCDENST00000435422.7 linkuse as main transcriptc.781G>A p.Glu261Lys missense_variant 8/81 ENSP00000403003.2 Q92629-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461320
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
726950
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000882
Hom.:
0

ClinVar

Significance: Likely pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Autosomal recessive limb-girdle muscular dystrophy type 2F Pathogenic:1
Pathogenic, no assertion criteria providedliterature onlyOMIMNov 01, 1998- -
Dilated cardiomyopathy 1L Pathogenic:1
Likely pathogenic, criteria provided, single submitterclinical testingBaylor GeneticsMar 18, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.97
BayesDel_addAF
Pathogenic
0.47
D
BayesDel_noAF
Pathogenic
0.44
CADD
Pathogenic
32
DANN
Pathogenic
1.0
DEOGEN2
Pathogenic
0.90
D;.
Eigen
Uncertain
0.65
Eigen_PC
Uncertain
0.65
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Pathogenic
0.97
D;D
M_CAP
Uncertain
0.28
D
MetaRNN
Pathogenic
0.97
D;D
MetaSVM
Uncertain
0.65
D
MutationAssessor
Uncertain
2.4
M;.
PrimateAI
Uncertain
0.78
T
PROVEAN
Uncertain
-2.8
D;D
REVEL
Pathogenic
0.84
Sift
Uncertain
0.0030
D;D
Sift4G
Uncertain
0.0050
D;D
Polyphen
1.0
D;D
Vest4
0.79
MutPred
0.89
Gain of methylation at E261 (P = 0.0016);.;
MVP
0.92
MPC
0.53
ClinPred
0.99
D
GERP RS
4.9
Varity_R
0.71
gMVP
0.77

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs121909297; hg19: chr5-156186312; COSMIC: COSV61911296; COSMIC: COSV61911296; API