rs1801193

chr5-156344569-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000337.6(SGCD):c.84T>C(p.Tyr28=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 1,610,812 control chromosomes in the GnomAD database, including 164,446 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.41 (13481 hom., cov: 31)
  • Exomes 𝑓: 0.45 (150965 hom.)
• Consequence: SGCD NM_000337.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:14
• Conservation: PhyloP100: -0.334

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]

LOC124901120 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 5-156344569-T-C is Benign according to our data. Variant chr5-156344569-T-C is described in ClinVar as [Benign]. Clinvar id is 48125.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-156344569-T-C is described in Lovd as [Benign]. Variant chr5-156344569-T-C is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=-0.334 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.773 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SGCD	NM_000337.6	c.84T>C	p.Tyr28=	synonymous_variant	3/9	ENST00000337851.9
LOC124901120	XR_007059016.1	n.234+2884A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SGCD	ENST00000337851.9	c.84T>C	p.Tyr28=	synonymous_variant	3/9	1	NM_000337.6	P4
SGCD	ENST00000435422.7	c.81T>C	p.Tyr27=	synonymous_variant	2/8	1		A1
SGCD	ENST00000517913.5	c.84T>C	p.Tyr28=	synonymous_variant	5/10	5
SGCD	ENST00000524347.2	c.84T>C	p.Tyr28=	synonymous_variant, NMD_transcript_variant	3/6	5

Frequencies

GnomAD3 genomes AF: 0.408 AC: 61982 AN: 151814 Hom.: 13485 Cov.: 31

Gnomad AFR AF: 0.269

Gnomad AMI AF: 0.454

Gnomad AMR AF: 0.446

Gnomad ASJ AF: 0.480

Gnomad EAS AF: 0.794

Gnomad SAS AF: 0.550

Gnomad FIN AF: 0.462

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.432

Gnomad OTH AF: 0.429

GnomAD3 exomes AF: 0.469 AC: 115786 AN: 247132 Hom.: 28607 AF XY: 0.475 AC XY: 63771 AN XY: 134124

Gnomad AFR exome AF: 0.265

Gnomad AMR exome AF: 0.444

Gnomad ASJ exome AF: 0.486

Gnomad EAS exome AF: 0.778

Gnomad SAS exome AF: 0.556

Gnomad FIN exome AF: 0.464

Gnomad NFE exome AF: 0.431

Gnomad OTH exome AF: 0.459

GnomAD4 exome AF: 0.448 AC: 654227 AN: 1458880 Hom.: 150965 Cov.: 34 AF XY: 0.452 AC XY: 328256 AN XY: 725632

Gnomad4 AFR exome AF: 0.258

Gnomad4 AMR exome AF: 0.446

Gnomad4 ASJ exome AF: 0.481

Gnomad4 EAS exome AF: 0.795

Gnomad4 SAS exome AF: 0.557

Gnomad4 FIN exome AF: 0.456

Gnomad4 NFE exome AF: 0.432

Gnomad4 OTH exome AF: 0.457

GnomAD4 genome AF: 0.408 AC: 62003 AN: 151932 Hom.: 13481 Cov.: 31 AF XY: 0.417 AC XY: 30989 AN XY: 74242

Gnomad4 AFR AF: 0.269

Gnomad4 AMR AF: 0.446

Gnomad4 ASJ AF: 0.480

Gnomad4 EAS AF: 0.793

Gnomad4 SAS AF: 0.548

Gnomad4 FIN AF: 0.462

Gnomad4 NFE AF: 0.432

Gnomad4 OTH AF: 0.434

Alfa AF: 0.422 Hom.: 7058

Bravo AF: 0.401

Asia WGS AF: 0.625 AC: 2174 AN: 3478

EpiCase AF: 0.442

EpiControl AF: 0.442

ClinVar

Significance: Benign

Submissions summary: Benign:14

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:9

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Dec 04, 2008	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Apr 13, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Aug 15, 2013	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 25, 2012	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Aug 25, 2017	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

Autosomal recessive limb-girdle muscular dystrophy type 2F Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -

Qualitative or quantitative defects of delta-sarcoglycan Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Inborn genetic diseases Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 22, 2015

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Limb-Girdle Muscular Dystrophy, Recessive Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
Cadd	Benign	1.1
Dann	Benign	0.48

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: rs1801193; hg19: chr5-155771579; COSMIC: COSV61912922;