rs749205073

Variant names:

• chr17-50167694-C-G
• NM_000023.4:c.270C>G

Your query was ambiguous. Multiple possible variants found:

• chr17-50167694-C-G
• chr17-50167694-C-T

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_000023.4(SGCA):​c.270C>G​(p.Tyr90*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SGCA NM_000023.4 stop_gained
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: -2.50

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]

ACMG classification

Verdict is Pathogenic. Variant got 12 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 17-50167694-C-G is Pathogenic according to our data. Variant chr17-50167694-C-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 3240445.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SGCA	NM_000023.4	c.270C>G	p.Tyr90*	stop_gained	Exon 3 of 10	ENST00000262018.8	NP_000014.1
SGCA	NM_001135697.3	c.270C>G	p.Tyr90*	stop_gained	Exon 3 of 8		NP_001129169.1
SGCA	NR_135553.2	n.306C>G		non_coding_transcript_exon_variant	Exon 3 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SGCA	ENST00000262018.8	c.270C>G	p.Tyr90*	stop_gained	Exon 3 of 10	1	NM_000023.4	ENSP00000262018.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Autosomal recessive limb-girdle muscular dystrophy type 2D Pathogenic:1

Dec 27, 2023

Baylor Genetics

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.62	D
BayesDel_noAF	Pathogenic	0.53
CADD	Benign	23
DANN	Uncertain	0.99
Eigen	Benign	-0.084
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.26	N
Vest4		0.76
GERP RS		-3.9

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-48245055;