rs10503497

Variant names:

• chr8-14424873-A-C
• rs10503497
• NM_139167.4:c.235-100669T>G

Your query was ambiguous. Multiple possible variants found:

• chr8-14424873-A-C
• chr8-14424873-A-G
• chr8-14424873-A-T

Variant summary

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

The NM_139167.4(SGCZ):​c.235-100669T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 152,166 control chromosomes in the GnomAD database, including 3,832 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 0.21 (3832 hom., cov: 32)
• Consequence: SGCZ NM_139167.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25
• 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=-1.04).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SGCZ	NM_139167.4	c.235-100669T>G		intron_variant	Intron 2 of 7	ENST00000382080.6	NP_631906.2
SGCZ	NM_001322879.2	c.234+129859T>G		intron_variant	Intron 2 of 6		NP_001309808.1
SGCZ	NM_001322880.2	c.235-100669T>G		intron_variant	Intron 2 of 6		NP_001309809.1
SGCZ	NM_001322881.2	c.13-100669T>G		intron_variant	Intron 2 of 6		NP_001309810.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SGCZ	ENST00000382080.6	c.235-100669T>G		intron_variant	Intron 2 of 7	5	NM_139167.4	ENSP00000371512.1
SGCZ	ENST00000421524.6	c.195+129859T>G		intron_variant	Intron 1 of 5	1		ENSP00000405224.2

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31373 AN: 152046 Hom.: 3834 Cov.: 32

Gnomad AFR AF: 0.0810

Gnomad AMI AF: 0.234

Gnomad AMR AF: 0.209

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.0640

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.235

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.288

Gnomad OTH AF: 0.223

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

GnomAD4 genome AF: 0.206 AC: 31376 AN: 152166 Hom.: 3832 Cov.: 32 AF XY: 0.200 AC XY: 14868 AN XY: 74358

African (AFR) AF: 0.0809 AC: 3361 AN: 41532

American (AMR) AF: 0.209 AC: 3195 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.313 AC: 1084 AN: 3468

East Asian (EAS) AF: 0.0641 AC: 332 AN: 5178

South Asian (SAS) AF: 0.125 AC: 602 AN: 4830

European-Finnish (FIN) AF: 0.235 AC: 2485 AN: 10580

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.288 AC: 19569 AN: 67990

Other (OTH) AF: 0.221 AC: 467 AN: 2110

Alfa AF: 0.264 Hom.: 7940

Bravo AF: 0.202

Asia WGS AF: 0.114 AC: 400 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	0.60
DANN	Benign	0.41
PhyloP100		-1.3
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: rs10503497; hg19: chr8-14282382;