chr5-156647468-G-A

Variant names:

• chr5-156647468-G-A
• rs10071079
• NM_000337.6:c.507G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_000337.6(SGCD):​c.507G>A​(p.Ala169Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00121 in 1,580,166 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. A169A) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0063 (11 hom., cov: 33)
  • Exomes 𝑓: 0.00067 (10 hom.)
• Consequence: SGCD NM_000337.6 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:15
• Conservation: PhyloP100: -0.663
• Publications: 0 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

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 5-156647468-G-A is Benign according to our data. Variant chr5-156647468-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 48120.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.663 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00628 (956/152218) while in subpopulation AFR AF = 0.0217 (902/41550). AF 95% confidence interval is 0.0205. There are 11 homozygotes in GnomAd4. There are 440 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 11 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000337.6. 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.507G>A	p.Ala169Ala	synonymous	Exon 7 of 9	NP_000328.2
	SGCD	NM_001128209.2		c.504G>A	p.Ala168Ala	synonymous	Exon 6 of 8	NP_001121681.1	Q92629-1
	SGCD	NM_172244.3		c.507G>A	p.Ala169Ala	synonymous	Exon 7 of 8	NP_758447.1	Q92629-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGCD	ENST00000337851.9	TSL:1 MANE Select	c.507G>A	p.Ala169Ala	synonymous	Exon 7 of 9	ENSP00000338343.4	Q92629-2
	SGCD	ENST00000435422.7	TSL:1	c.504G>A	p.Ala168Ala	synonymous	Exon 6 of 8	ENSP00000403003.2	Q92629-1
	SGCD	ENST00000959784.1		c.558G>A	p.Ala186Ala	synonymous	Exon 8 of 10	ENSP00000629843.1

Frequencies

GnomAD3 genomes AF: 0.00628 AC: 955 AN: 152100 Hom.: 11 Cov.: 33

Gnomad AFR AF: 0.0217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00190

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.00383

GnomAD2 exomes AF: 0.00139 AC: 284 AN: 204028 AF XY: 0.00117

Gnomad AFR exome AF: 0.0203

Gnomad AMR exome AF: 0.000773

Gnomad ASJ exome AF: 0.000109

Gnomad EAS exome AF: 0.0000661

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000137

Gnomad OTH exome AF: 0.000191

GnomAD4 exome AF: 0.000672 AC: 960 AN: 1427948 Hom.: 10 Cov.: 29 AF XY: 0.000574 AC XY: 406 AN XY: 707038

African (AFR) AF: 0.0217 AC: 713 AN: 32906

American (AMR) AF: 0.000965 AC: 39 AN: 40410

Ashkenazi Jewish (ASJ) AF: 0.0000785 AC: 2 AN: 25474

East Asian (EAS) AF: 0.0000259 AC: 1 AN: 38632

South Asian (SAS) AF: 0.000147 AC: 12 AN: 81750

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51512

Middle Eastern (MID) AF: 0.000175 AC: 1 AN: 5722

European-Non Finnish (NFE) AF: 0.000101 AC: 110 AN: 1092432

Other (OTH) AF: 0.00139 AC: 82 AN: 59110

GnomAD4 genome AF: 0.00628 AC: 956 AN: 152218 Hom.: 11 Cov.: 33 AF XY: 0.00591 AC XY: 440 AN XY: 74398

African (AFR) AF: 0.0217 AC: 902 AN: 41550

American (AMR) AF: 0.00190 AC: 29 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000235 AC: 16 AN: 68018

Other (OTH) AF: 0.00379 AC: 8 AN: 2112

Alfa AF: 0.00232 Hom.: 7

Bravo AF: 0.00687

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	3	not specified (3)
-	-	2	Autosomal recessive limb-girdle muscular dystrophy type 2F (2)
-	-	1	Autosomal recessive limb-girdle muscular dystrophy type 2F;C1847667:Dilated cardiomyopathy 1L (1)
-	-	1	Cardiomyopathy (1)
-	-	1	Dilated cardiomyopathy 1L (1)
-	-	1	Inborn genetic diseases (1)
-	-	1	Limb-girdle muscular dystrophy, recessive (1)
-	-	1	Qualitative or quantitative defects of delta-sarcoglycan (1)
-	-	1	SGCD-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	5.8
DANN	Benign	0.65
PhyloP100		-0.66
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs10071079; hg19: chr5-156074478; COSMIC: COSV100548508;