5-156327182-C-G

Position:

• chr5-156327182-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000337.6(SGCD):​c.-94C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 152,358 control chromosomes in the GnomAD database, including 11,991 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.38 (11974 hom., cov: 34)
  • Exomes 𝑓: 0.42 (17 hom.)
• Consequence: SGCD NM_000337.6 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 2.06

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 5-156327182-C-G is Benign according to our data. Variant chr5-156327182-C-G is described in ClinVar as [Benign]. Clinvar id is 48114.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-156327182-C-G is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.77 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SGCD	NM_000337.6	c.-94C>G		5_prime_UTR_variant	1/9	ENST00000337851.9
LOC124901120	XR_007059016.1	n.234+20271G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SGCD	ENST00000337851.9	c.-94C>G		5_prime_UTR_variant	1/9	1	NM_000337.6	P4
SGCD	ENST00000435422.7	c.-51C>G		5_prime_UTR_variant	1/8	1		A1
SGCD	ENST00000517913.5	c.-43-2352C>G		intron_variant		5
SGCD	ENST00000524347.2	c.-94C>G		5_prime_UTR_variant, NMD_transcript_variant	1/6	5

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57448 AN: 152100 Hom.: 11979 Cov.: 34

Gnomad AFR AF: 0.212

Gnomad AMI AF: 0.447

Gnomad AMR AF: 0.432

Gnomad ASJ AF: 0.457

Gnomad EAS AF: 0.790

Gnomad SAS AF: 0.522

Gnomad FIN AF: 0.408

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.415

Gnomad OTH AF: 0.396

GnomAD4 exome AF: 0.421 AC: 59 AN: 140 Hom.: 17 Cov.: 0 AF XY: 0.444 AC XY: 48 AN XY: 108

Gnomad4 AMR exome AF: 0.500

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 0.750

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.417

Gnomad4 OTH exome AF: 0.333

GnomAD4 genome AF: 0.377 AC: 57460 AN: 152218 Hom.: 11974 Cov.: 34 AF XY: 0.385 AC XY: 28684 AN XY: 74408

Gnomad4 AFR AF: 0.212

Gnomad4 AMR AF: 0.432

Gnomad4 ASJ AF: 0.457

Gnomad4 EAS AF: 0.790

Gnomad4 SAS AF: 0.521

Gnomad4 FIN AF: 0.408

Gnomad4 NFE AF: 0.415

Gnomad4 OTH AF: 0.401

Alfa AF: 0.236 Hom.: 558

Bravo AF: 0.371

Asia WGS AF: 0.607 AC: 2109 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Sep 16, 2011

- -

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

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Feb 08, 2023

- -

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

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Dilated cardiomyopathy 1L Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Feb 08, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	7.0
DANN	Benign	0.67

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: rs13170573; hg19: chr5-155754192;