rs10503506

Variant names:

• chr8-14655169-A-G
• rs10503506
• NM_139167.4:c.40-100243T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_139167.4(SGCZ):​c.40-100243T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 152,032 control chromosomes in the GnomAD database, including 2,359 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 0.16 (2359 hom., cov: 32)
• Consequence: SGCZ NM_139167.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0130
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SGCZ	NM_139167.4	c.40-100243T>C		intron_variant	Intron 1 of 7	ENST00000382080.6	NP_631906.2
SGCZ	NM_001322879.2	c.40-100243T>C		intron_variant	Intron 1 of 6		NP_001309808.1
SGCZ	NM_001322880.2	c.40-100243T>C		intron_variant	Intron 1 of 6		NP_001309809.1
SGCZ	NM_001322881.2	c.-89-100243T>C		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.40-100243T>C		intron_variant	Intron 1 of 7	5	NM_139167.4	ENSP00000371512.1

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24374 AN: 151914 Hom.: 2356 Cov.: 32

Gnomad AFR AF: 0.0684

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.230

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.0544

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.206

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.154

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

GnomAD4 genome AF: 0.160 AC: 24396 AN: 152032 Hom.: 2359 Cov.: 32 AF XY: 0.161 AC XY: 11966 AN XY: 74318

African (AFR) AF: 0.0684 AC: 2839 AN: 41486

American (AMR) AF: 0.231 AC: 3514 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.227 AC: 787 AN: 3460

East Asian (EAS) AF: 0.0545 AC: 282 AN: 5170

South Asian (SAS) AF: 0.103 AC: 495 AN: 4826

European-Finnish (FIN) AF: 0.206 AC: 2181 AN: 10570

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.203 AC: 13807 AN: 67974

Other (OTH) AF: 0.153 AC: 322 AN: 2102

Alfa AF: 0.194 Hom.: 1800

Bravo AF: 0.160

Asia WGS AF: 0.0960 AC: 334 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.5
DANN	Benign	0.76
PhyloP100		0.013
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: rs10503506; hg19: chr8-14512678;