rs45559835

Positions:

chr5-156508698-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000337.6(SGCD):c.290G>A(p.Arg97Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0543 in 1,568,098 control chromosomes in the GnomAD database, including 2,622 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. R97R) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.042 ( 187 hom., cov: 32)

Exomes 𝑓: 0.056 ( 2435 hom. )

Consequence

SGCD
NM_000337.6 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:18

Conservation

PhyloP100: 4.20

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0041366518).

BP6

Variant 5-156508698-G-A is Benign according to our data. Variant chr5-156508698-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 48117.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-156508698-G-A is described in Lovd as [Benign]. Variant chr5-156508698-G-A is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0616 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SGCD	NM_000337.6 linkuse as main transcript	c.290G>A	p.Arg97Gln	missense_variant	4/9	ENST00000337851.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SGCD	ENST00000337851.9 linkuse as main transcript	c.290G>A	p.Arg97Gln	missense_variant	4/9	1	NM_000337.6	P4	Q92629-2
SGCD	ENST00000435422.7 linkuse as main transcript	c.287G>A	p.Arg96Gln	missense_variant	3/8	1		A1	Q92629-1
SGCD	ENST00000517913.5 linkuse as main transcript	c.290G>A	p.Arg97Gln	missense_variant	6/10	5			Q92629-3
SGCD	ENST00000524347.2 linkuse as main transcript	c.*154G>A		3_prime_UTR_variant, NMD_transcript_variant	5/6	5

Frequencies

GnomAD3 genomes

AF:

0.0420

AC:

6393

AN:

152062

Hom.:

188

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0102

Gnomad AMI

AF:

0.0504

Gnomad AMR

AF:

0.0466

Gnomad ASJ

AF:

0.0833

Gnomad EAS

AF:

0.000962

Gnomad SAS

AF:

0.0193

Gnomad FIN

AF:

0.0403

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0632

Gnomad OTH

AF:

0.0435

GnomAD3 exomes

AF:

0.0453

AC:

10602

AN:

234230

Hom.:

292

AF XY:

0.0454

AC XY:

5760

AN XY:

126922

show subpopulations

Gnomad AFR exome

AF:

0.00945

Gnomad AMR exome

AF:

0.0342

Gnomad ASJ exome

AF:

0.0783

Gnomad EAS exome

AF:

0.0000586

Gnomad SAS exome

AF:

0.0204

Gnomad FIN exome

AF:

0.0444

Gnomad NFE exome

AF:

0.0636

Gnomad OTH exome

AF:

0.0513

GnomAD4 exome

AF:

0.0557

AC:

78825

AN:

1415918

Hom.:

2435

Cov.:

AF XY:

0.0549

AC XY:

38702

AN XY:

705496

show subpopulations

Gnomad4 AFR exome

AF:

0.00818

Gnomad4 AMR exome

AF:

0.0333

Gnomad4 ASJ exome

AF:

0.0767

Gnomad4 EAS exome

AF:

0.0000762

Gnomad4 SAS exome

AF:

0.0205

Gnomad4 FIN exome

AF:

0.0429

Gnomad4 NFE exome

AF:

0.0630

Gnomad4 OTH exome

AF:

0.0528

GnomAD4 genome

AF:

0.0420

AC:

6389

AN:

152180

Hom.:

187

Cov.:

AF XY:

0.0409

AC XY:

3044

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.0101

Gnomad4 AMR

AF:

0.0465

Gnomad4 ASJ

AF:

0.0833

Gnomad4 EAS

AF:

0.000965

Gnomad4 SAS

AF:

0.0191

Gnomad4 FIN

AF:

0.0403

Gnomad4 NFE

AF:

0.0632

Gnomad4 OTH

AF:

0.0431

Alfa

AF:

0.0582

Hom.:

444

Bravo

AF:

0.0409

TwinsUK

AF:

0.0591

AC:

219

ALSPAC

AF:

0.0620

AC:

239

ESP6500AA

AF:

0.0119

AC:

ESP6500EA

AF:

0.0642

AC:

527

ExAC

AF:

0.0436

AC:

5262

Asia WGS

AF:

0.0120

AC:

AN:

3476

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:18

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:8

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jul 12, 2012	- -
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	research	Biesecker Lab/Clinical Genomics Section, National Institutes of Health	Jun 24, 2013	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Jan 20, 2009	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

Autosomal recessive limb-girdle muscular dystrophy type 2F

Benign:3

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Apr 13, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Feb 08, 2023	- -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	This variant is associated with the following publications: (PMID: 10974018, 26968544, 28401079) -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 03, 2023	- -
Likely benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

Limb-girdle muscular dystrophy, recessive

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Qualitative or quantitative defects of delta-sarcoglycan

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 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. -

Dilated cardiomyopathy 1L

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Feb 08, 2023

- -

Cardiovascular phenotype

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 19, 2012

This alteration is classified as benign based on a combination of the following: 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

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.13

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Pathogenic

0.89

.;D;.

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.91

D;D;D

MetaRNN

Benign

0.0041

T;T;T

MetaSVM

Uncertain

-0.12

MutationAssessor

Benign

1.8

.;L;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.52

PROVEAN

Uncertain

-3.2

D;D;D

REVEL

Uncertain

0.42

Sift

Benign

0.062

T;D;D

Sift4G

Uncertain

0.032

D;D;D

Polyphen

0.97

D;P;P

Vest4

0.28

MPC

0.38

ClinPred

0.029

GERP RS

5.5

Varity_R

0.35

gMVP

0.63

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