chr5-156508693-G-T

Position:

• chr5-156508693-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_000337.6(SGCD):​c.285G>T​(p.Gln95His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Uncertain significancein ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SGCD NM_000337.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.62

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28080678).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SGCD	NM_000337.6	c.285G>T	p.Gln95His	missense_variant	4/9	ENST00000337851.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SGCD	ENST00000337851.9	c.285G>T	p.Gln95His	missense_variant	4/9	1	NM_000337.6	P4
SGCD	ENST00000435422.7	c.282G>T	p.Gln94His	missense_variant	3/8	1		A1
SGCD	ENST00000517913.5	c.285G>T	p.Gln95His	missense_variant	6/10	5
SGCD	ENST00000524347.2	c.*149G>T		3_prime_UTR_variant, NMD_transcript_variant	5/6	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000423 AC: 1 AN: 236622 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 128208

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000913

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 25

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.0075	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	19
DANN	Benign	0.29
DEOGEN2	Uncertain	0.50	.;D;.
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.0014
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.69	T;T;T
M_CAP	Benign	0.052	D
MetaRNN	Benign	0.28	T;T;T
MetaSVM	Uncertain	-0.22	T
MutationAssessor	Benign	0.14	.;N;.
MutationTaster	Benign	0.95	D;D;D;D
PrimateAI	Benign	0.32	T
PROVEAN	Benign	0.45	N;N;N
REVEL	Benign	0.22
Sift	Benign	0.76	T;T;T
Sift4G	Benign	0.65	T;T;T
Polyphen		0.43	B;P;P
Vest4		0.35
MutPred		0.30		.;Loss of ubiquitination at K91 (P = 0.1486);.;
MVP		0.83
MPC		0.16
ClinPred		0.26	T
GERP RS		3.7
Varity_R		0.042
gMVP		0.51

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: rs1421460814; hg19: chr5-155935703;