chr5-156647468-G-T

Variant names:

• chr5-156647468-G-T
• rs10071079
• NM_000337.6:c.507G>T
• SGCD p.Ala169Ala

Variant summary

Our verdict is

Likely benign

-5 Likely Benign

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

. The variant received -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_000337.6(SGCD):​c.507G>T​(p.Ala169Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000014 in 1,427,964 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. The gene SGCD is included in the ClinGen Criteria Specification Registry.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SGCD NM_000337.6 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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: PanelApp Australia, ClinGen
• autosomal recessive limb-girdle muscular dystrophy type 2F

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Myriad Women's Health, Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet
• familial isolated dilated cardiomyopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• dilated cardiomyopathy 1L

  Inheritance: AD Classification: LIMITED, NO_KNOWN Submitted by: Ambry Genetics, ClinGen

ACMG classification

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

Our verdict: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 5-156647468-G-T is Benign according to our data. Variant chr5-156647468-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 799206.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.663 with no splicing effect.

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>T	p.Ala169Ala	synonymous	Exon 7 of 9	NP_000328.2
	SGCD	NM_001128209.2		c.504G>T	p.Ala168Ala	synonymous	Exon 6 of 8	NP_001121681.1	Q92629-1
	SGCD	NM_172244.3		c.507G>T	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>T	p.Ala169Ala	synonymous	Exon 7 of 9	ENSP00000338343.4	Q92629-2
	SGCD	ENST00000435422.7	TSL:1	c.504G>T	p.Ala168Ala	synonymous	Exon 6 of 8	ENSP00000403003.2	Q92629-1
	SGCD	ENST00000959784.1		c.558G>T	p.Ala186Ala	synonymous	Exon 8 of 10	ENSP00000629843.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000140 AC: 2 AN: 1427964 Hom.: 0 Cov.: 29 AF XY: 0.00000141 AC XY: 1 AN XY: 707048

African (AFR) AF: 0.00 AC: 0 AN: 32922

American (AMR) AF: 0.00 AC: 0 AN: 40410

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25474

East Asian (EAS) AF: 0.00 AC: 0 AN: 38630

South Asian (SAS) AF: 0.00 AC: 0 AN: 81750

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5722

European-Non Finnish (NFE) AF: 0.00000183 AC: 2 AN: 1092434

Other (OTH) AF: 0.00 AC: 0 AN: 59110

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Autosomal recessive limb-girdle muscular dystrophy type 2F (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	0.67
DANN	Benign	0.63
PhyloP100		-0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs10071079;

hg19: chr5-156074478;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline