5-156344590-G-C

Variant names:

• chr5-156344590-G-C
• rs193922392
• NM_000337.6:c.105G>C

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.105G>C​(p.Leu35Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000407 in 1,612,480 control chromosomes in the GnomAD database, including 2 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. L35L) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0023 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00021 (2 hom.)
• Consequence: SGCD NM_000337.6 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: 1.36
• Publications: 1 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 5-156344590-G-C is Benign according to our data. Variant chr5-156344590-G-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 36771.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.36 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00229 (348/152226) while in subpopulation AFR AF = 0.00809 (336/41528). AF 95% confidence interval is 0.00738. There are 0 homozygotes in GnomAd4. There are 158 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 2 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.105G>C	p.Leu35Leu	synonymous	Exon 3 of 9	NP_000328.2
	SGCD	NM_001128209.2		c.102G>C	p.Leu34Leu	synonymous	Exon 2 of 8	NP_001121681.1	Q92629-1
	SGCD	NM_172244.3		c.105G>C	p.Leu35Leu	synonymous	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.105G>C	p.Leu35Leu	synonymous	Exon 3 of 9	ENSP00000338343.4	Q92629-2
	SGCD	ENST00000435422.7	TSL:1	c.102G>C	p.Leu34Leu	synonymous	Exon 2 of 8	ENSP00000403003.2	Q92629-1
	SGCD	ENST00000959784.1		c.105G>C	p.Leu35Leu	synonymous	Exon 3 of 10	ENSP00000629843.1

Frequencies

GnomAD3 genomes AF: 0.00227 AC: 346 AN: 152108 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00807

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000459

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.000529 AC: 131 AN: 247582 AF XY: 0.000380

Gnomad AFR exome AF: 0.00772

Gnomad AMR exome AF: 0.000324

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000889

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000212 AC: 309 AN: 1460254 Hom.: 2 Cov.: 32 AF XY: 0.000180 AC XY: 131 AN XY: 726356

African (AFR) AF: 0.00730 AC: 244 AN: 33420

American (AMR) AF: 0.000292 AC: 13 AN: 44556

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39624

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 85870

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53392

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1111182

Other (OTH) AF: 0.000763 AC: 46 AN: 60324

GnomAD4 genome AF: 0.00229 AC: 348 AN: 152226 Hom.: 0 Cov.: 32 AF XY: 0.00212 AC XY: 158 AN XY: 74428

African (AFR) AF: 0.00809 AC: 336 AN: 41528

American (AMR) AF: 0.000458 AC: 7 AN: 15286

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68022

Other (OTH) AF: 0.00189 AC: 4 AN: 2114

Alfa AF: 0.000810 Hom.: 0

Bravo AF: 0.00263

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	6.0
DANN	Benign	0.78
PhyloP100		1.4

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: rs193922392; hg19: chr5-155771600;