rs1801193

Positions:

chr5-156344569-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:14

Conservation

PhyloP100: -0.334

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]

SGCD links:

LOC124901120 (HGNC:):

LOC124901120 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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	Protein	UniProt
SGCD	NM_000337.6 linkuse as main transcript	c.84T>C	p.Tyr28=	synonymous_variant	3/9	ENST00000337851.9	NP_000328.2
LOC124901120	XR_007059016.1 linkuse as main transcript	n.234+2884A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SGCD	ENST00000337851.9 linkuse as main transcript	c.84T>C	p.Tyr28=	synonymous_variant	3/9	1	NM_000337.6	ENSP00000338343	P4	Q92629-2
SGCD	ENST00000435422.7 linkuse as main transcript	c.81T>C	p.Tyr27=	synonymous_variant	2/8	1		ENSP00000403003	A1	Q92629-1
SGCD	ENST00000517913.5 linkuse as main transcript	c.84T>C	p.Tyr28=	synonymous_variant	5/10	5		ENSP00000429378		Q92629-3
SGCD	ENST00000524347.2 linkuse as main transcript	c.84T>C	p.Tyr28=	synonymous_variant, NMD_transcript_variant	3/6	5		ENSP00000430794

Frequencies

GnomAD3 genomes

AF:

0.408

AC:

61982

AN:

151814

Hom.:

13485

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.452

AC XY:

328256

AN XY:

725632

show subpopulations

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.:

AF XY:

0.417

AC XY:

30989

AN XY:

74242

show subpopulations

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

LINK: link

Submissions by phenotype

not specified

Benign:9

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Aug 25, 2017	- -
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, 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	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Aug 15, 2013	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Apr 13, 2017	- -

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	Labcorp Genetics (formerly Invitae), Labcorp	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. -

Limb-girdle muscular dystrophy, recessive

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

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. -

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

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over