rs4383970

chr8-15108680-A-T

Variant summary

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

The NM_139167.4(SGCZ):c.39+128905T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.48 in 151,998 control chromosomes in the GnomAD database, including 18,556 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 0.48 (18556 hom., cov: 32)
• Consequence: SGCZ NM_139167.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.167

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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.656 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SGCZ	NM_139167.4	c.39+128905T>A		intron_variant		ENST00000382080.6
SGCZ	NM_001322879.2	c.39+128905T>A		intron_variant
SGCZ	NM_001322880.2	c.39+128905T>A		intron_variant
SGCZ	NM_001322881.2	c.-90+128905T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SGCZ	ENST00000382080.6	c.39+128905T>A		intron_variant		5	NM_139167.4	P1

Frequencies

GnomAD3 genomes AF: 0.480 AC: 72922 AN: 151880 Hom.: 18520 Cov.: 32

Gnomad AFR AF: 0.662

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.347

Gnomad ASJ AF: 0.488

Gnomad EAS AF: 0.385

Gnomad SAS AF: 0.501

Gnomad FIN AF: 0.387

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.422

Gnomad OTH AF: 0.458

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

GnomAD4 genome AF: 0.480 AC: 73020 AN: 151998 Hom.: 18556 Cov.: 32 AF XY: 0.479 AC XY: 35555 AN XY: 74282

Gnomad4 AFR AF: 0.663

Gnomad4 AMR AF: 0.347

Gnomad4 ASJ AF: 0.488

Gnomad4 EAS AF: 0.386

Gnomad4 SAS AF: 0.501

Gnomad4 FIN AF: 0.387

Gnomad4 NFE AF: 0.422

Gnomad4 OTH AF: 0.462

Alfa AF: 0.457 Hom.: 2019

Bravo AF: 0.484

Asia WGS AF: 0.430 AC: 1497 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.82
Dann	Benign	0.44

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: rs4383970; hg19: chr8-14966189;