rs7717393

Variant names:

• chr5-156326904-C-G
• rs7717393
• ENST00000435422.7:c.-329C>G

Your query was ambiguous. Multiple possible variants found:

• chr5-156326904-C-G
• chr5-156326904-C-A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The ENST00000435422.7(SGCD):​c.-329C>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 0.0759 in 152,334 control chromosomes in the GnomAD database, including 454 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.076 (454 hom., cov: 33)
  • Exomes 𝑓: 0.10 (0 hom.)
• Consequence: SGCD ENST00000435422.7 5_prime_UTR
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:2
• Conservation: PhyloP100: -1.50
• Publications: 8 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, STRONG Submitted by: ClinGen, PanelApp Australia
• autosomal recessive limb-girdle muscular dystrophy type 2F

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

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

  Inheritance: AD Classification: NO_KNOWN 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 5-156326904-C-G is Benign according to our data. Variant chr5-156326904-C-G is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 48112.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.178 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000435422.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGCD	ENST00000435422.7	TSL:1	c.-329C>G		5_prime_UTR	Exon 1 of 8	ENSP00000403003.2	Q92629-1
	SGCD	ENST00000959782.1		c.-43-2630C>G		intron	N/A	ENSP00000629841.1
	SGCD	ENST00000517913.5	TSL:5	c.-43-2630C>G		intron	N/A	ENSP00000429378.1	Q92629-3

Frequencies

GnomAD3 genomes AF: 0.0758 AC: 11528 AN: 152146 Hom.: 454 Cov.: 33

Gnomad AFR AF: 0.0783

Gnomad AMI AF: 0.0647

Gnomad AMR AF: 0.0808

Gnomad ASJ AF: 0.0836

Gnomad EAS AF: 0.0469

Gnomad SAS AF: 0.186

Gnomad FIN AF: 0.0449

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0717

Gnomad OTH AF: 0.0836

GnomAD4 exome AF: 0.100 AC: 7 AN: 70 Hom.: 0 Cov.: 0 AF XY: 0.0962 AC XY: 5 AN XY: 52

African (AFR) AF: 0.250 AC: 1 AN: 4

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.103 AC: 6 AN: 58

Other (OTH) AF: 0.00 AC: 0 AN: 4

GnomAD4 genome AF: 0.0759 AC: 11552 AN: 152264 Hom.: 454 Cov.: 33 AF XY: 0.0773 AC XY: 5758 AN XY: 74454

African (AFR) AF: 0.0782 AC: 3249 AN: 41532

American (AMR) AF: 0.0816 AC: 1249 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0836 AC: 290 AN: 3468

East Asian (EAS) AF: 0.0472 AC: 244 AN: 5174

South Asian (SAS) AF: 0.188 AC: 906 AN: 4828

European-Finnish (FIN) AF: 0.0449 AC: 476 AN: 10612

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0717 AC: 4878 AN: 68028

Other (OTH) AF: 0.0827 AC: 175 AN: 2116

Alfa AF: 0.0334 Hom.: 15

Bravo AF: 0.0761

Asia WGS AF: 0.116 AC: 404 AN: 3478

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)
-	1	-	Qualitative or quantitative defects of delta-sarcoglycan (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.30
DANN	Benign	0.73
PhyloP100		-1.5
PromoterAI		-0.025	Neutral
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs7717393; hg19: chr5-155753914;