8-14996272-A-T

Position:

• chr8-14996272-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+241313T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.56 in 152,090 control chromosomes in the GnomAD database, including 26,788 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 0.56 (26788 hom., cov: 33)
• Consequence: SGCZ NM_139167.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0170

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.859 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SGCZ	NM_139167.4	c.39+241313T>A		intron_variant		ENST00000382080.6	NP_631906.2
SGCZ	NM_001322879.2	c.39+241313T>A		intron_variant			NP_001309808.1
SGCZ	NM_001322880.2	c.39+241313T>A		intron_variant			NP_001309809.1
SGCZ	NM_001322881.2	c.-90+241313T>A		intron_variant			NP_001309810.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SGCZ	ENST00000382080.6	c.39+241313T>A		intron_variant		5	NM_139167.4	ENSP00000371512.1

Frequencies

GnomAD3 genomes AF: 0.560 AC: 85043 AN: 151968 Hom.: 26726 Cov.: 33

Gnomad AFR AF: 0.866

Gnomad AMI AF: 0.662

Gnomad AMR AF: 0.450

Gnomad ASJ AF: 0.359

Gnomad EAS AF: 0.473

Gnomad SAS AF: 0.540

Gnomad FIN AF: 0.517

Gnomad MID AF: 0.401

Gnomad NFE AF: 0.423

Gnomad OTH AF: 0.504

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

GnomAD4 genome AF: 0.560 AC: 85163 AN: 152090 Hom.: 26788 Cov.: 33 AF XY: 0.561 AC XY: 41671 AN XY: 74344

Gnomad4 AFR AF: 0.867

Gnomad4 AMR AF: 0.449

Gnomad4 ASJ AF: 0.359

Gnomad4 EAS AF: 0.474

Gnomad4 SAS AF: 0.540

Gnomad4 FIN AF: 0.517

Gnomad4 NFE AF: 0.423

Gnomad4 OTH AF: 0.509

Alfa AF: 0.343 Hom.: 861

Bravo AF: 0.566

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	3.7
DANN	Benign	0.36

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: rs4427170; hg19: chr8-14853781;