17-50167819-C-T

Position:

• chr17-50167819-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000023.4(SGCA):​c.312+83C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.837 in 1,552,088 control chromosomes in the GnomAD database, including 544,610 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.84 (53165 hom., cov: 32)
  • Exomes 𝑓: 0.84 (491445 hom.)
• Consequence: SGCA NM_000023.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.610

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 17-50167819-C-T is Benign according to our data. Variant chr17-50167819-C-T is described in ClinVar as [Benign]. Clinvar id is 669840.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-50167819-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.933 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SGCA	NM_000023.4	c.312+83C>T		intron_variant		ENST00000262018.8	NP_000014.1
SGCA	NM_001135697.3	c.312+83C>T		intron_variant			NP_001129169.1
SGCA	NR_135553.2	n.348+83C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SGCA	ENST00000262018.8	c.312+83C>T		intron_variant		1	NM_000023.4	ENSP00000262018	P1

Frequencies

GnomAD3 genomes AF: 0.836 AC: 127071 AN: 152060 Hom.: 53132 Cov.: 32

Gnomad AFR AF: 0.827

Gnomad AMI AF: 0.786

Gnomad AMR AF: 0.805

Gnomad ASJ AF: 0.854

Gnomad EAS AF: 0.956

Gnomad SAS AF: 0.859

Gnomad FIN AF: 0.849

Gnomad MID AF: 0.858

Gnomad NFE AF: 0.834

Gnomad OTH AF: 0.862

GnomAD4 exome AF: 0.837 AC: 1172235 AN: 1399910 Hom.: 491445 Cov.: 23 AF XY: 0.838 AC XY: 585395 AN XY: 698652

Gnomad4 AFR exome AF: 0.821

Gnomad4 AMR exome AF: 0.781

Gnomad4 ASJ exome AF: 0.862

Gnomad4 EAS exome AF: 0.955

Gnomad4 SAS exome AF: 0.864

Gnomad4 FIN exome AF: 0.840

Gnomad4 NFE exome AF: 0.833

Gnomad4 OTH exome AF: 0.843

GnomAD4 genome AF: 0.836 AC: 127163 AN: 152178 Hom.: 53165 Cov.: 32 AF XY: 0.836 AC XY: 62198 AN XY: 74384

Gnomad4 AFR AF: 0.827

Gnomad4 AMR AF: 0.805

Gnomad4 ASJ AF: 0.854

Gnomad4 EAS AF: 0.956

Gnomad4 SAS AF: 0.859

Gnomad4 FIN AF: 0.849

Gnomad4 NFE AF: 0.834

Gnomad4 OTH AF: 0.860

Alfa AF: 0.833 Hom.: 48032

Bravo AF: 0.832

Asia WGS AF: 0.897 AC: 3118 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

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

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jun 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.22
DANN	Benign	0.38

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

Publications

LitVar

Other links and lift over

dbSNP: rs2696297; hg19: chr17-48245180;