rs10503511

Positions:

• chr8-14667314-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_139167.4(SGCZ):​c.40-112388C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 151,890 control chromosomes in the GnomAD database, including 11,182 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.34 (11182 hom., cov: 31)
• Consequence: SGCZ NM_139167.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.406

Genes affected

SGCZ (HGNC:14075): (sarcoglycan zeta) The zeta-sarcoglycan gene measures over 465 kb and localizes to 8p22. This protein is part of the sarcoglycan complex, a group of 6 proteins. The sarcoglycans are all N-glycosylated transmembrane proteins with a short intra-cellular domain, a single transmembrane region and a large extra-cellular domain containing a carboxyl-terminal cluster with several conserved cysteine residues. The sarcoglycan complex is part of the dystrophin-associated glycoprotein complex (DGC), which bridges the inner cytoskeleton and the extra-cellular matrix. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.621 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SGCZ	NM_139167.4	c.40-112388C>T		intron_variant		ENST00000382080.6
SGCZ	NM_001322879.2	c.40-112388C>T		intron_variant
SGCZ	NM_001322880.2	c.40-112388C>T		intron_variant
SGCZ	NM_001322881.2	c.-89-112388C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SGCZ	ENST00000382080.6	c.40-112388C>T		intron_variant		5	NM_139167.4	P1

Frequencies

GnomAD3 genomes AF: 0.338 AC: 51270 AN: 151772 Hom.: 11167 Cov.: 31

Gnomad AFR AF: 0.627

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.262

Gnomad ASJ AF: 0.182

Gnomad EAS AF: 0.296

Gnomad SAS AF: 0.254

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.214

Gnomad OTH AF: 0.307

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.338 AC: 51342 AN: 151890 Hom.: 11182 Cov.: 31 AF XY: 0.335 AC XY: 24900 AN XY: 74226

Gnomad4 AFR AF: 0.627

Gnomad4 AMR AF: 0.262

Gnomad4 ASJ AF: 0.182

Gnomad4 EAS AF: 0.296

Gnomad4 SAS AF: 0.255

Gnomad4 FIN AF: 0.246

Gnomad4 NFE AF: 0.214

Gnomad4 OTH AF: 0.306

Alfa AF: 0.247 Hom.: 2289

Bravo AF: 0.353

Asia WGS AF: 0.295 AC: 1027 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.36
DANN	Benign	0.45

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: rs10503511; hg19: chr8-14524823;