17-50175443-T-C

Variant names:

• chr17-50175443-T-C
• rs2696288
• NM_000023.4:c.*6T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000023.4(SGCA):​c.*6T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.953 in 1,612,590 control chromosomes in the GnomAD database, including 733,968 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.92 (64324 hom., cov: 35)
  • Exomes 𝑓: 0.96 (669644 hom.)
• Consequence: SGCA NM_000023.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -3.25
• Publications: 14 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 17-50175443-T-C is Benign according to our data. Variant chr17-50175443-T-C is described in ClinVar as Benign. ClinVar VariationId is 167679.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

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.*6T>C		3_prime_UTR	Exon 9 of 10	NP_000014.1
	SGCA	NR_135553.2		n.997T>C		non_coding_transcript_exon	Exon 8 of 9
	SGCA	NM_001135697.3		c.*6T>C		3_prime_UTR	Exon 7 of 8	NP_001129169.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGCA	ENST00000262018.8	TSL:1 MANE Select	c.*6T>C		3_prime_UTR	Exon 9 of 10	ENSP00000262018.3
	SGCA	ENST00000344627.10	TSL:1	c.*6T>C		3_prime_UTR	Exon 7 of 8	ENSP00000345522.6
	ENSG00000253730	ENST00000504307.4	TSL:1	n.548-3266A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.916 AC: 139433 AN: 152204 Hom.: 64284 Cov.: 35

Gnomad AFR AF: 0.796

Gnomad AMI AF: 0.985

Gnomad AMR AF: 0.952

Gnomad ASJ AF: 0.956

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.990

Gnomad FIN AF: 0.964

Gnomad MID AF: 0.959

Gnomad NFE AF: 0.958

Gnomad OTH AF: 0.929

GnomAD2 exomes AF: 0.958 AC: 236484 AN: 246726 AF XY: 0.962

Gnomad AFR exome AF: 0.793

Gnomad AMR exome AF: 0.971

Gnomad ASJ exome AF: 0.953

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 0.967

Gnomad NFE exome AF: 0.961

Gnomad OTH exome AF: 0.960

GnomAD4 exome AF: 0.957 AC: 1397766 AN: 1460268 Hom.: 669644 Cov.: 43 AF XY: 0.959 AC XY: 696574 AN XY: 726422

African (AFR) AF: 0.789 AC: 26398 AN: 33462

American (AMR) AF: 0.969 AC: 43315 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.954 AC: 24912 AN: 26126

East Asian (EAS) AF: 1.00 AC: 39699 AN: 39700

South Asian (SAS) AF: 0.989 AC: 85259 AN: 86166

European-Finnish (FIN) AF: 0.967 AC: 50572 AN: 52298

Middle Eastern (MID) AF: 0.973 AC: 5599 AN: 5752

European-Non Finnish (NFE) AF: 0.958 AC: 1064544 AN: 1111700

Other (OTH) AF: 0.952 AC: 57468 AN: 60368

GnomAD4 genome AF: 0.916 AC: 139528 AN: 152322 Hom.: 64324 Cov.: 35 AF XY: 0.919 AC XY: 68473 AN XY: 74494

African (AFR) AF: 0.796 AC: 33069 AN: 41530

American (AMR) AF: 0.952 AC: 14583 AN: 15314

Ashkenazi Jewish (ASJ) AF: 0.956 AC: 3318 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5187 AN: 5188

South Asian (SAS) AF: 0.990 AC: 4783 AN: 4832

European-Finnish (FIN) AF: 0.964 AC: 10247 AN: 10628

Middle Eastern (MID) AF: 0.959 AC: 282 AN: 294

European-Non Finnish (NFE) AF: 0.958 AC: 65195 AN: 68038

Other (OTH) AF: 0.930 AC: 1966 AN: 2114

Alfa AF: 0.941 Hom.: 51929

Bravo AF: 0.909

Asia WGS AF: 0.984 AC: 3423 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not specified (5)
-	-	2	Autosomal recessive limb-girdle muscular dystrophy type 2D (2)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.052
DANN	Benign	0.53
PhyloP100		-3.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2696288; hg19: chr17-48252804;