8-15108680-A-T

Variant names:

• chr8-15108680-A-T
• rs4383970
• NM_139167.4:c.39+128905T>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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]

ENSG00000301307 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SGCZ	NM_139167.4	c.39+128905T>A		intron_variant	Intron 1 of 7	ENST00000382080.6	NP_631906.2
SGCZ	NM_001322879.2	c.39+128905T>A		intron_variant	Intron 1 of 6		NP_001309808.1
SGCZ	NM_001322880.2	c.39+128905T>A		intron_variant	Intron 1 of 6		NP_001309809.1
SGCZ	NM_001322881.2	c.-90+128905T>A		intron_variant	Intron 1 of 6		NP_001309810.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SGCZ	ENST00000382080.6	c.39+128905T>A		intron_variant	Intron 1 of 7	5	NM_139167.4	ENSP00000371512.1
ENSG00000301307	ENST00000777843.1	n.89+11790T>A		intron_variant	Intron 1 of 1

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

African (AFR) AF: 0.663 AC: 27458 AN: 41446

American (AMR) AF: 0.347 AC: 5294 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.488 AC: 1692 AN: 3470

East Asian (EAS) AF: 0.386 AC: 1992 AN: 5166

South Asian (SAS) AF: 0.501 AC: 2411 AN: 4816

European-Finnish (FIN) AF: 0.387 AC: 4076 AN: 10544

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.422 AC: 28690 AN: 67968

Other (OTH) AF: 0.462 AC: 976 AN: 2112

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
PhyloP100		-0.17
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4383970; hg19: chr8-14966189;