17-50165951-C-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The XR_934833.3(LOC105371818):n.340+67G>T variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00929 in 1,045,858 control chromosomes in the GnomAD database, including 54 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0072 (9 hom., cov: 32)
  • Exomes 𝑓: 0.0097 (45 hom.)
• Consequence: LOC105371818 XR_934833.3 intron, non_coding_transcript
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.31

Genes affected

LOC105371818 (HGNC:):

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 Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 17-50165951-C-A is Benign according to our data. Variant chr17-50165951-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 1179547.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd at 9 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC105371818	XR_934833.3	n.340+67G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SGCA	ENST00000513942.5	n.103+1635C>A		intron_variant, non_coding_transcript_variant		3
SGCA	ENST00000514934.1			upstream_gene_variant		4

Frequencies

GnomAD3 genomes AF: 0.00718 AC: 1093 AN: 152128 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.00193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00537

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00186

Gnomad FIN AF: 0.0117

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0113

Gnomad OTH AF: 0.00813

GnomAD4 exome AF: 0.00965 AC: 8624 AN: 893612 Hom.: 45 Cov.: 12 AF XY: 0.00939 AC XY: 4387 AN XY: 467066

Gnomad4 AFR exome AF: 0.00159

Gnomad4 AMR exome AF: 0.00456

Gnomad4 ASJ exome AF: 0.00452

Gnomad4 EAS exome AF: 0.0000269

Gnomad4 SAS exome AF: 0.00219

Gnomad4 FIN exome AF: 0.00999

Gnomad4 NFE exome AF: 0.0121

Gnomad4 OTH exome AF: 0.00888

GnomAD4 genome AF: 0.00718 AC: 1093 AN: 152246 Hom.: 9 Cov.: 32 AF XY: 0.00716 AC XY: 533 AN XY: 74422

Gnomad4 AFR AF: 0.00193

Gnomad4 AMR AF: 0.00536

Gnomad4 ASJ AF: 0.00346

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00186

Gnomad4 FIN AF: 0.0117

Gnomad4 NFE AF: 0.0113

Gnomad4 OTH AF: 0.00805

Alfa AF: 0.00974 Hom.: 0

Bravo AF: 0.00661

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2023	SGCA: BS1, BS2 -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 26, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
Cadd	Benign	9.4
Dann	Benign	0.75

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs75145501; hg19: chr17-48243312; COSMIC: COSV56251727;