5-156326973-A-T

Variant names:

• chr5-156326973-A-T
• rs7725121
• ENST00000435422.7:c.-260A>T

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The ENST00000524347.2(SGCD):​n.-303A>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0679 in 152,408 control chromosomes in the GnomAD database, including 381 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.068 (381 hom., cov: 33)
  • Exomes 𝑓: 0.081 (0 hom.)
• Consequence: SGCD ENST00000524347.2 non_coding_transcript_exon
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 2.43
• Publications: 5 publications found

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 Gene-Disease associations (from GenCC):

• autosomal recessive limb-girdle muscular dystrophy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• autosomal recessive limb-girdle muscular dystrophy type 2F

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Myriad Women’s Health, Ambry Genetics
• familial isolated dilated cardiomyopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• dilated cardiomyopathy

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen
• dilated cardiomyopathy 1L

  Inheritance: AD Classification: NO_KNOWN Submitted by: Ambry Genetics

LOC124901120 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 5-156326973-A-T is Benign according to our data. Variant chr5-156326973-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 48111.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SGCD	NM_000337.6	c.-303A>T		upstream_gene_variant		ENST00000337851.9	NP_000328.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SGCD	ENST00000337851.9	c.-303A>T		upstream_gene_variant		1	NM_000337.6	ENSP00000338343.4

Frequencies

GnomAD3 genomes AF: 0.0678 AC: 10326 AN: 152228 Hom.: 381 Cov.: 33

Gnomad AFR AF: 0.0518

Gnomad AMI AF: 0.0647

Gnomad AMR AF: 0.0766

Gnomad ASJ AF: 0.0838

Gnomad EAS AF: 0.0472

Gnomad SAS AF: 0.186

Gnomad FIN AF: 0.0447

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0713

Gnomad OTH AF: 0.0764

GnomAD4 exome AF: 0.0806 AC: 5 AN: 62 Hom.: 0 Cov.: 0 AF XY: 0.0833 AC XY: 4 AN XY: 48

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.250 AC: 1 AN: 4

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0833 AC: 3 AN: 36

Other (OTH) AF: 0.0714 AC: 1 AN: 14

GnomAD4 genome AF: 0.0679 AC: 10348 AN: 152346 Hom.: 381 Cov.: 33 AF XY: 0.0698 AC XY: 5202 AN XY: 74508

African (AFR) AF: 0.0517 AC: 2149 AN: 41576

American (AMR) AF: 0.0775 AC: 1186 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.0838 AC: 291 AN: 3472

East Asian (EAS) AF: 0.0475 AC: 246 AN: 5180

South Asian (SAS) AF: 0.187 AC: 905 AN: 4830

European-Finnish (FIN) AF: 0.0447 AC: 475 AN: 10626

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0713 AC: 4852 AN: 68028

Other (OTH) AF: 0.0756 AC: 160 AN: 2116

Alfa AF: 0.0703 Hom.: 43

Bravo AF: 0.0669

Asia WGS AF: 0.115 AC: 400 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

Apr 20, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

Feb 08, 2023

Genome-Nilou Lab

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Qualitative or quantitative defects of delta-sarcoglycan Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Dilated cardiomyopathy 1L Benign:1

Feb 08, 2023

Genome-Nilou Lab

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	17
DANN	Benign	0.92
PhyloP100		2.4
PromoterAI		-0.25	Neutral
Mutation Taster		=294/6	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7725121; hg19: chr5-155753983;