8-15142603-T-C

Variant names:

• chr8-15142603-T-C
• rs17575278
• NM_139167.4:c.39+94982A>G

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+94982A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.061 in 151,972 control chromosomes in the GnomAD database, including 345 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 0.061 (345 hom., cov: 30)
• Consequence: SGCZ NM_139167.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.236
• Publications: 2 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139167.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGCZ	NM_139167.4	MANE Select	c.39+94982A>G		intron	N/A	NP_631906.2	Q96LD1-2
	SGCZ	NM_001322879.2		c.39+94982A>G		intron	N/A	NP_001309808.1
	SGCZ	NM_001322880.2		c.39+94982A>G		intron	N/A	NP_001309809.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGCZ	ENST00000382080.6	TSL:5 MANE Select	c.39+94982A>G		intron	N/A	ENSP00000371512.1	Q96LD1-2

Frequencies

GnomAD3 genomes AF: 0.0611 AC: 9281 AN: 151854 Hom.: 347 Cov.: 30

Gnomad AFR AF: 0.0163

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0746

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.0691

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.0609

Gnomad MID AF: 0.124

Gnomad NFE AF: 0.0770

Gnomad OTH AF: 0.0738

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

GnomAD4 genome AF: 0.0610 AC: 9275 AN: 151972 Hom.: 345 Cov.: 30 AF XY: 0.0622 AC XY: 4619 AN XY: 74262

African (AFR) AF: 0.0163 AC: 674 AN: 41456

American (AMR) AF: 0.0745 AC: 1136 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.130 AC: 452 AN: 3470

East Asian (EAS) AF: 0.0690 AC: 354 AN: 5128

South Asian (SAS) AF: 0.118 AC: 567 AN: 4806

European-Finnish (FIN) AF: 0.0609 AC: 644 AN: 10568

Middle Eastern (MID) AF: 0.127 AC: 37 AN: 292

European-Non Finnish (NFE) AF: 0.0770 AC: 5236 AN: 67972

Other (OTH) AF: 0.0730 AC: 154 AN: 2110

Alfa AF: 0.0744 Hom.: 834

Bravo AF: 0.0593

Asia WGS AF: 0.0760 AC: 263 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.0
DANN	Benign	0.53
PhyloP100		0.24
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: rs17575278; hg19: chr8-15000112;