chr5-156594940-G-C

Position:

• chr5-156594940-G-C

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2 PP3_Strong PP5

The NM_000337.6(SGCD):​c.391G>C​(p.Ala131Pro) variant causes a missense change. 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 (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SGCD NM_000337.6 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 4.22

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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.957
• PP5: Variant 5-156594940-G-C is Pathogenic according to our data. Variant chr5-156594940-G-C is described in ClinVar as [Pathogenic]. Clinvar id is 8177.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-156594940-G-C is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SGCD	NM_000337.6	c.391G>C	p.Ala131Pro	missense_variant	6/9	ENST00000337851.9	NP_000328.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SGCD	ENST00000337851.9	c.391G>C	p.Ala131Pro	missense_variant	6/9	1	NM_000337.6	ENSP00000338343.4
SGCD	ENST00000435422.7	c.388G>C	p.Ala130Pro	missense_variant	5/8	1		ENSP00000403003.2
SGCD	ENST00000517913.5	c.391G>C	p.Ala131Pro	missense_variant	8/10	5		ENSP00000429378.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Autosomal recessive limb-girdle muscular dystrophy type 2F Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Sep 01, 2009

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.94
BayesDel_addAF	Pathogenic	0.36	D
BayesDel_noAF	Pathogenic	0.28
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.75	.;D;.
Eigen	Benign	0.027
Eigen_PC	Benign	0.034
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.73	T;T;T
M_CAP	Uncertain	0.20	D
MetaRNN	Pathogenic	0.96	D;D;D
MetaSVM	Uncertain	0.54	D
MutationAssessor	Benign	1.4	.;L;.
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-1.6	N;N;N
REVEL	Pathogenic	0.69
Sift	Benign	0.22	T;T;T
Sift4G	Benign	0.27	T;T;T
Polyphen		0.99	D;P;P
Vest4		0.91
MutPred		0.80		.;Loss of helix (P = 0.0123);.;
MVP		0.95
MPC		0.30
ClinPred		0.76	D
GERP RS		3.9
Varity_R		0.36
gMVP		0.81

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

Other links and lift over

dbSNP: rs267607045; hg19: chr5-156021950;