5-155967220-C-T

Variant names:

• chr5-155967220-C-T
• rs17053082
• ENST00000517913.5:c.-282+96796C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000517913.5(SGCD):​c.-282+96796C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.056 in 151,958 control chromosomes in the GnomAD database, including 260 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.056 (260 hom., cov: 32)
• Consequence: SGCD ENST00000517913.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.50
• Publications: 16 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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0805 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SGCD	XM_017009724.2	c.-207-156636C>T		intron_variant	Intron 1 of 9		XP_016865213.1
SGCD	XM_047417518.1	c.-263-67880C>T		intron_variant	Intron 2 of 11		XP_047273474.1
SGCD	XM_047417519.1	c.-208+96796C>T		intron_variant	Intron 2 of 10		XP_047273475.1
SGCD	XM_047417520.1	c.-164-156636C>T		intron_variant	Intron 1 of 8		XP_047273476.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SGCD	ENST00000517913.5	c.-282+96796C>T		intron_variant	Intron 1 of 9	5		ENSP00000429378.1

Frequencies

GnomAD3 genomes AF: 0.0560 AC: 8497 AN: 151840 Hom.: 259 Cov.: 32

Gnomad AFR AF: 0.0646

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0450

Gnomad ASJ AF: 0.0824

Gnomad EAS AF: 0.0303

Gnomad SAS AF: 0.0874

Gnomad FIN AF: 0.0369

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0549

Gnomad OTH AF: 0.0608

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0560 AC: 8507 AN: 151958 Hom.: 260 Cov.: 32 AF XY: 0.0563 AC XY: 4179 AN XY: 74282

African (AFR) AF: 0.0647 AC: 2681 AN: 41436

American (AMR) AF: 0.0449 AC: 685 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.0824 AC: 286 AN: 3472

East Asian (EAS) AF: 0.0304 AC: 156 AN: 5138

South Asian (SAS) AF: 0.0874 AC: 420 AN: 4804

European-Finnish (FIN) AF: 0.0369 AC: 391 AN: 10602

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0549 AC: 3731 AN: 67942

Other (OTH) AF: 0.0592 AC: 125 AN: 2110

Alfa AF: 0.0574 Hom.: 652

Bravo AF: 0.0569

Asia WGS AF: 0.0450 AC: 157 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.6
DANN	Benign	0.44
PhyloP100		1.5
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs17053082; hg19: chr5-155394230;