8-14608172-C-T

Position:

• chr8-14608172-C-T

Variant summary

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

The NM_139167.4(SGCZ):​c.40-53246G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.781 in 151,906 control chromosomes in the GnomAD database, including 46,685 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 0.78 (46685 hom., cov: 30)
• Consequence: SGCZ NM_139167.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0390

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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.822 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SGCZ	NM_139167.4	c.40-53246G>A		intron_variant		ENST00000382080.6
SGCZ	NM_001322879.2	c.40-53246G>A		intron_variant
SGCZ	NM_001322880.2	c.40-53246G>A		intron_variant
SGCZ	NM_001322881.2	c.-89-53246G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SGCZ	ENST00000382080.6	c.40-53246G>A		intron_variant		5	NM_139167.4	P1

Frequencies

GnomAD3 genomes AF: 0.781 AC: 118519 AN: 151790 Hom.: 46668 Cov.: 30

Gnomad AFR AF: 0.677

Gnomad AMI AF: 0.849

Gnomad AMR AF: 0.805

Gnomad ASJ AF: 0.843

Gnomad EAS AF: 0.797

Gnomad SAS AF: 0.670

Gnomad FIN AF: 0.865

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.828

Gnomad OTH AF: 0.778

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

GnomAD4 genome AF: 0.781 AC: 118579 AN: 151906 Hom.: 46685 Cov.: 30 AF XY: 0.782 AC XY: 58064 AN XY: 74244

Gnomad4 AFR AF: 0.677

Gnomad4 AMR AF: 0.806

Gnomad4 ASJ AF: 0.843

Gnomad4 EAS AF: 0.797

Gnomad4 SAS AF: 0.668

Gnomad4 FIN AF: 0.865

Gnomad4 NFE AF: 0.828

Gnomad4 OTH AF: 0.771

Alfa AF: 0.804 Hom.: 19388

Bravo AF: 0.775

Asia WGS AF: 0.686 AC: 2388 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.2
DANN	Benign	0.40

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: rs7837164; hg19: chr8-14465681;