rs45559835

Variant names:

• chr5-156508698-G-A
• rs45559835
• NM_000337.6:c.290G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-156508698-G-A
• chr5-156508698-G-C
• chr5-156508698-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000337.6(SGCD):​c.290G>A​(p.Arg97Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0543 in 1,568,098 control chromosomes in the GnomAD database, including 2,622 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. R97R) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.042 (187 hom., cov: 32)
  • Exomes 𝑓: 0.056 (2435 hom.)
• Consequence: SGCD NM_000337.6 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:19
• Conservation: PhyloP100: 4.20
• Publications: 18 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0041366518).
• BP6: Variant 5-156508698-G-A is Benign according to our data. Variant chr5-156508698-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 48117.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0616 is higher than 0.05.

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.290G>A	p.Arg97Gln	missense	Exon 4 of 9	NP_000328.2
	SGCD	NM_001128209.2		c.287G>A	p.Arg96Gln	missense	Exon 3 of 8	NP_001121681.1	Q92629-1
	SGCD	NM_172244.3		c.290G>A	p.Arg97Gln	missense	Exon 4 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.290G>A	p.Arg97Gln	missense	Exon 4 of 9	ENSP00000338343.4	Q92629-2
	SGCD	ENST00000435422.7	TSL:1	c.287G>A	p.Arg96Gln	missense	Exon 3 of 8	ENSP00000403003.2	Q92629-1
	SGCD	ENST00000959784.1		c.341G>A	p.Arg114Gln	missense	Exon 5 of 10	ENSP00000629843.1

Frequencies

GnomAD3 genomes AF: 0.0420 AC: 6393 AN: 152062 Hom.: 188 Cov.: 32

Gnomad AFR AF: 0.0102

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.0466

Gnomad ASJ AF: 0.0833

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.0193

Gnomad FIN AF: 0.0403

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0632

Gnomad OTH AF: 0.0435

GnomAD2 exomes AF: 0.0453 AC: 10602 AN: 234230 AF XY: 0.0454

Gnomad AFR exome AF: 0.00945

Gnomad AMR exome AF: 0.0342

Gnomad ASJ exome AF: 0.0783

Gnomad EAS exome AF: 0.0000586

Gnomad FIN exome AF: 0.0444

Gnomad NFE exome AF: 0.0636

Gnomad OTH exome AF: 0.0513

GnomAD4 exome AF: 0.0557 AC: 78825 AN: 1415918 Hom.: 2435 Cov.: 24 AF XY: 0.0549 AC XY: 38702 AN XY: 705496

African (AFR) AF: 0.00818 AC: 263 AN: 32168

American (AMR) AF: 0.0333 AC: 1382 AN: 41554

Ashkenazi Jewish (ASJ) AF: 0.0767 AC: 1933 AN: 25206

East Asian (EAS) AF: 0.0000762 AC: 3 AN: 39380

South Asian (SAS) AF: 0.0205 AC: 1687 AN: 82116

European-Finnish (FIN) AF: 0.0429 AC: 2277 AN: 53050

Middle Eastern (MID) AF: 0.0417 AC: 235 AN: 5636

European-Non Finnish (NFE) AF: 0.0630 AC: 67942 AN: 1078070

Other (OTH) AF: 0.0528 AC: 3103 AN: 58738

GnomAD4 genome AF: 0.0420 AC: 6389 AN: 152180 Hom.: 187 Cov.: 32 AF XY: 0.0409 AC XY: 3044 AN XY: 74400

African (AFR) AF: 0.0101 AC: 421 AN: 41532

American (AMR) AF: 0.0465 AC: 711 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0833 AC: 289 AN: 3470

East Asian (EAS) AF: 0.000965 AC: 5 AN: 5184

South Asian (SAS) AF: 0.0191 AC: 92 AN: 4820

European-Finnish (FIN) AF: 0.0403 AC: 427 AN: 10590

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0632 AC: 4297 AN: 67982

Other (OTH) AF: 0.0431 AC: 91 AN: 2112

Alfa AF: 0.0559 Hom.: 987

Bravo AF: 0.0409

TwinsUK AF: 0.0591 AC: 219

ALSPAC AF: 0.0620 AC: 239

ESP6500AA AF: 0.0119 AC: 44

ESP6500EA AF: 0.0642 AC: 527

ExAC AF: 0.0436 AC: 5262

Asia WGS AF: 0.0120 AC: 42 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	8	not specified (8)
-	-	4	not provided (4)
-	-	3	Autosomal recessive limb-girdle muscular dystrophy type 2F (3)
-	-	1	Cardiovascular phenotype (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	0.11
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	24
DANN	Pathogenic	1.0
DEOGEN2	Pathogenic	0.89	D
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.91	D
MetaRNN	Benign	0.0041	T
MetaSVM	Uncertain	-0.12	T
MutationAssessor	Benign	1.8	L
PhyloP100		4.2
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-3.2	D
REVEL	Uncertain	0.42
Sift	Benign	0.062	T
Sift4G	Uncertain	0.032	D
Polyphen		0.97	D
Vest4		0.28
MPC		0.38
ClinPred		0.029	T
GERP RS		5.5
Varity_R		0.35
gMVP		0.63
Mutation Taster		=99/1	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: rs45559835; hg19: chr5-155935708;