17-50170597-G-A

Variant names:

• chr17-50170597-G-A
• rs577470269
• NM_000023.4:c.957-43G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS1

The NM_000023.4(SGCA):​c.957-43G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00019 in 1,554,356 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00021 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00019 (1 hom.)
• Consequence: SGCA NM_000023.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0190
• 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 Submitted by: ClinGen
• autosomal recessive limb-girdle muscular dystrophy type 2D

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

ENSG00000253730 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 17-50170597-G-A is Benign according to our data. Variant chr17-50170597-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 254722.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. GnomAdExome4 allele frequency = 0.000188 (263/1402058) while in subpopulation AMR AF = 0.00653 (236/36126). AF 95% confidence interval is 0.00585. There are 1 homozygotes in GnomAdExome4. There are 112 alleles in the male GnomAdExome4 subpopulation. Median coverage is 30. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000023.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGCA	NM_000023.4	MANE Select	c.957-43G>A		intron	N/A	NP_000014.1
	SGCA	NM_001135697.3		c.585-43G>A		intron	N/A	NP_001129169.1
	SGCA	NR_135553.2		n.784-43G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGCA	ENST00000262018.8	TSL:1 MANE Select	c.957-43G>A		intron	N/A	ENSP00000262018.3
	SGCA	ENST00000344627.10	TSL:1	c.585-43G>A		intron	N/A	ENSP00000345522.6
	SGCA	ENST00000683544.1		n.568G>A		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.000210 AC: 32 AN: 152180 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00177

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000957

GnomAD2 exomes AF: 0.00133 AC: 216 AN: 162244 AF XY: 0.00105

Gnomad AFR exome AF: 0.000107

Gnomad AMR exome AF: 0.00816

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000839

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00175

GnomAD4 exome AF: 0.000188 AC: 263 AN: 1402058 Hom.: 1 Cov.: 30 AF XY: 0.000162 AC XY: 112 AN XY: 691970

African (AFR) AF: 0.00 AC: 0 AN: 31814

American (AMR) AF: 0.00653 AC: 236 AN: 36126

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25228

East Asian (EAS) AF: 0.000193 AC: 7 AN: 36180

South Asian (SAS) AF: 0.00 AC: 0 AN: 79582

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49572

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5692

European-Non Finnish (NFE) AF: 0.0000111 AC: 12 AN: 1079710

Other (OTH) AF: 0.000138 AC: 8 AN: 58154

GnomAD4 genome AF: 0.000210 AC: 32 AN: 152298 Hom.: 1 Cov.: 32 AF XY: 0.000175 AC XY: 13 AN XY: 74472

African (AFR) AF: 0.0000481 AC: 2 AN: 41544

American (AMR) AF: 0.00176 AC: 27 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68030

Other (OTH) AF: 0.000947 AC: 2 AN: 2112

Alfa AF: 0.000391 Hom.: 0

Bravo AF: 0.000710

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.5
DANN	Benign	0.36
PhyloP100		0.019
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs577470269; hg19: chr17-48247958;