rs7725121

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 ENST00000435422.7(SGCD):​c.-260A>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0679 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 ENST00000435422.7 5_prime_UTR
• 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, 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 -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 Benign/Likely_benign. ClinVar VariationId 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.

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
	SGCD	NM_000337.6	MANE Select	c.-303A>T		upstream_gene	N/A	NP_000328.2
	SGCD	NM_001128209.2		c.-260A>T		upstream_gene	N/A	NP_001121681.1	Q92629-1
	SGCD	NM_172244.3		c.-303A>T		upstream_gene	N/A	NP_758447.1	Q92629-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGCD	ENST00000435422.7	TSL:1	c.-260A>T		5_prime_UTR	Exon 1 of 8	ENSP00000403003.2	Q92629-1
	SGCD	ENST00000959782.1		c.-43-2561A>T		intron	N/A	ENSP00000629841.1
	SGCD	ENST00000517913.5	TSL:5	c.-43-2561A>T		intron	N/A	ENSP00000429378.1	Q92629-3

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

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Autosomal recessive limb-girdle muscular dystrophy type 2F (1)
-	-	1	Dilated cardiomyopathy 1L (1)
-	-	1	Limb-girdle muscular dystrophy, recessive (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	-0.41
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;