5-156344500-G-C

Variant names:

• chr5-156344500-G-C
• rs549319429
• NM_000337.6:c.15G>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_000337.6(SGCD):​c.15G>C​(p.Glu5Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000494 in 1,596,126 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict 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. E5E) has been classified as Likely benign. The gene SGCD is included in the ClinGen Criteria Specification Registry.

• Frequency:
  • Genomes: 𝑓 0.00024 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00052 (11 hom.)
• Consequence: SGCD NM_000337.6 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:13
• Conservation: PhyloP100: 0.893
• 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

Specifications for SGCD are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.010187924).
• BP6: Variant 5-156344500-G-C is Benign according to our data. Variant chr5-156344500-G-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 202085.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000237 (36/152062) while in subpopulation SAS AF = 0.00625 (30/4800). AF 95% confidence interval is 0.0045. There are 1 homozygotes in GnomAd4. There are 24 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 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.15G>C	p.Glu5Asp	missense	Exon 3 of 9	NP_000328.2
	SGCD	NM_001128209.2		c.12G>C	p.Glu4Asp	missense	Exon 2 of 8	NP_001121681.1	Q92629-1
	SGCD	NM_172244.3		c.15G>C	p.Glu5Asp	missense	Exon 3 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.15G>C	p.Glu5Asp	missense	Exon 3 of 9	ENSP00000338343.4	Q92629-2
	SGCD	ENST00000435422.7	TSL:1	c.12G>C	p.Glu4Asp	missense	Exon 2 of 8	ENSP00000403003.2	Q92629-1
	SGCD	ENST00000959784.1		c.15G>C	p.Glu5Asp	missense	Exon 3 of 10	ENSP00000629843.1

Frequencies

GnomAD3 genomes AF: 0.000230 AC: 35 AN: 151944 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000656

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00604

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00114 AC: 267 AN: 234906 AF XY: 0.00149

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000130

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000222

Gnomad OTH exome AF: 0.000716

GnomAD4 exome AF: 0.000521 AC: 753 AN: 1444064 Hom.: 11 Cov.: 31 AF XY: 0.000719 AC XY: 516 AN XY: 717662

African (AFR) AF: 0.0000308 AC: 1 AN: 32498

American (AMR) AF: 0.000119 AC: 5 AN: 41922

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25820

East Asian (EAS) AF: 0.0000261 AC: 1 AN: 38320

South Asian (SAS) AF: 0.00711 AC: 583 AN: 82018

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53298

Middle Eastern (MID) AF: 0.00141 AC: 8 AN: 5678

European-Non Finnish (NFE) AF: 0.000113 AC: 125 AN: 1104780

Other (OTH) AF: 0.000502 AC: 30 AN: 59730

GnomAD4 genome AF: 0.000237 AC: 36 AN: 152062 Hom.: 1 Cov.: 32 AF XY: 0.000323 AC XY: 24 AN XY: 74312

African (AFR) AF: 0.00 AC: 0 AN: 41478

American (AMR) AF: 0.0000655 AC: 1 AN: 15260

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00625 AC: 30 AN: 4800

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10570

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

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 67998

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000201 Hom.: 0

Bravo AF: 0.000110

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ExAC AF: 0.00138 AC: 167

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not provided (5)
-	-	2	Autosomal recessive limb-girdle muscular dystrophy type 2F (2)
-	-	2	not specified (2)
-	-	1	Cardiomyopathy (1)
-	-	1	Dilated cardiomyopathy 1L (1)
-	-	1	Limb-girdle muscular dystrophy, recessive (1)
-	-	1	Qualitative or quantitative defects of delta-sarcoglycan (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.46	T
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.64
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.078	D
MetaRNN	Benign	0.010	T
MetaSVM	Benign	-0.47	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		0.89
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.16
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.020	D
Polyphen		0.020	B
Vest4		0.47
MutPred		0.17		Loss of glycosylation at P2 (P = 0.0902)
MVP		0.48
MPC		0.54
ClinPred		0.047	T
GERP RS		-1.1
Varity_R		0.37
gMVP		0.60
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs549319429; hg19: chr5-155771510;