17-50165951-C-T

Variant names:

• chr17-50165951-C-T
• rs75145501
• ENST00000895791.1:c.-11-79C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000895791.1(SGCA):​c.-11-79C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000112 in 893,672 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000011 (0 hom.)
• Consequence: SGCA ENST00000895791.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.31
• Publications: 0 publications found

Genes affected

SGCA (HGNC:10805): (sarcoglycan alpha) This gene encodes a component of the dystrophin-glycoprotein complex (DGC), which is critical to the stability of muscle fiber membranes and to the linking of the actin cytoskeleton to the extracellular matrix. Its expression is thought to be restricted to striated muscle. Mutations in this gene result in type 2D autosomal recessive limb-girdle muscular dystrophy. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2008]

SGCA 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 2D

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Laboratory for Molecular Medicine, Myriad Women’s Health, Labcorp Genetics (formerly Invitae), Orphanet

ENSG00000253730 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000895791.1. 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
	SGCA	NM_000023.4	MANE Select	c.-90C>T		upstream_gene	N/A	NP_000014.1	A0A0S2Z4Q1
	SGCA	NM_001135697.3		c.-90C>T		upstream_gene	N/A	NP_001129169.1	A0A0S2Z4P8
	SGCA	NR_135553.2		n.-54C>T		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGCA	ENST00000895791.1		c.-11-79C>T		intron	N/A	ENSP00000565850.1
	SGCA	ENST00000895792.1		c.-11-79C>T		intron	N/A	ENSP00000565851.1
	SGCA	ENST00000513942.5	TSL:3	n.103+1635C>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000112 AC: 1 AN: 893672 Hom.: 0 Cov.: 12 AF XY: 0.00 AC XY: 0 AN XY: 467102

African (AFR) AF: 0.00 AC: 0 AN: 22620

American (AMR) AF: 0.00 AC: 0 AN: 42994

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21696

East Asian (EAS) AF: 0.0000269 AC: 1 AN: 37110

South Asian (SAS) AF: 0.00 AC: 0 AN: 73358

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52556

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3192

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 598818

Other (OTH) AF: 0.00 AC: 0 AN: 41328

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	10
DANN	Benign	0.74
PhyloP100		2.3
PromoterAI		0.13	Neutral

Splicing

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

Other links and lift over

dbSNP: rs75145501; hg19: chr17-48243312;