rs10503514

Variant names:

• chr8-14740708-A-G
• rs10503514
• NM_139167.4:c.40-185782T>C

Your query was ambiguous. Multiple possible variants found:

• chr8-14740708-A-G
• chr8-14740708-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.40-185782T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0265 in 152,110 control chromosomes in the GnomAD database, including 73 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 0.027 (73 hom., cov: 32)
• Consequence: SGCZ NM_139167.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.158
• 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]

ENSG00000305769 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0593 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SGCZ	NM_139167.4	c.40-185782T>C		intron_variant	Intron 1 of 7	ENST00000382080.6	NP_631906.2
SGCZ	NM_001322879.2	c.40-185782T>C		intron_variant	Intron 1 of 6		NP_001309808.1
SGCZ	NM_001322880.2	c.40-185782T>C		intron_variant	Intron 1 of 6		NP_001309809.1
SGCZ	NM_001322881.2	c.-89-185782T>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.40-185782T>C		intron_variant	Intron 1 of 7	5	NM_139167.4	ENSP00000371512.1
ENSG00000305769	ENST00000812855.1	n.304+204A>G		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.0265 AC: 4025 AN: 151992 Hom.: 73 Cov.: 32

Gnomad AFR AF: 0.0469

Gnomad AMI AF: 0.0253

Gnomad AMR AF: 0.0185

Gnomad ASJ AF: 0.0156

Gnomad EAS AF: 0.0183

Gnomad SAS AF: 0.0660

Gnomad FIN AF: 0.0172

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0155

Gnomad OTH AF: 0.0268

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

GnomAD4 genome AF: 0.0265 AC: 4036 AN: 152110 Hom.: 73 Cov.: 32 AF XY: 0.0266 AC XY: 1979 AN XY: 74382

African (AFR) AF: 0.0470 AC: 1951 AN: 41526

American (AMR) AF: 0.0186 AC: 283 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.0156 AC: 54 AN: 3470

East Asian (EAS) AF: 0.0182 AC: 94 AN: 5172

South Asian (SAS) AF: 0.0652 AC: 315 AN: 4830

European-Finnish (FIN) AF: 0.0172 AC: 183 AN: 10616

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0155 AC: 1056 AN: 67950

Other (OTH) AF: 0.0289 AC: 61 AN: 2114

Alfa AF: 0.00919 Hom.: 3

Bravo AF: 0.0268

Asia WGS AF: 0.0440 AC: 155 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.99
DANN	Benign	0.44
PhyloP100		-0.16
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: rs10503514; hg19: chr8-14598217;