8-14304694-G-A

Variant names:

• chr8-14304694-G-A
• rs10096683
• NM_139167.4:c.336+19409C>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.336+19409C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0484 in 152,104 control chromosomes in the GnomAD database, including 190 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 0.048 (190 hom., cov: 33)
• Consequence: SGCZ NM_139167.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00700
• Publications: 3 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.056 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SGCZ	NM_139167.4	c.336+19409C>T		intron_variant	Intron 3 of 7	ENST00000382080.6	NP_631906.2
SGCZ	NM_001322879.2	c.235-67015C>T		intron_variant	Intron 2 of 6		NP_001309808.1
SGCZ	NM_001322880.2	c.336+19409C>T		intron_variant	Intron 3 of 6		NP_001309809.1
SGCZ	NM_001322881.2	c.114+19409C>T		intron_variant	Intron 3 of 6		NP_001309810.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SGCZ	ENST00000382080.6	c.336+19409C>T		intron_variant	Intron 3 of 7	5	NM_139167.4	ENSP00000371512.1
SGCZ	ENST00000421524.6	c.196-67015C>T		intron_variant	Intron 1 of 5	1		ENSP00000405224.2

Frequencies

GnomAD3 genomes AF: 0.0484 AC: 7351 AN: 151986 Hom.: 189 Cov.: 33

Gnomad AFR AF: 0.0577

Gnomad AMI AF: 0.0659

Gnomad AMR AF: 0.0400

Gnomad ASJ AF: 0.0430

Gnomad EAS AF: 0.0174

Gnomad SAS AF: 0.0431

Gnomad FIN AF: 0.0446

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0475

Gnomad OTH AF: 0.0560

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

GnomAD4 genome AF: 0.0484 AC: 7365 AN: 152104 Hom.: 190 Cov.: 33 AF XY: 0.0476 AC XY: 3535 AN XY: 74342

African (AFR) AF: 0.0579 AC: 2403 AN: 41512

American (AMR) AF: 0.0399 AC: 609 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.0430 AC: 149 AN: 3466

East Asian (EAS) AF: 0.0174 AC: 90 AN: 5164

South Asian (SAS) AF: 0.0434 AC: 209 AN: 4818

European-Finnish (FIN) AF: 0.0446 AC: 472 AN: 10580

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0475 AC: 3228 AN: 67992

Other (OTH) AF: 0.0555 AC: 117 AN: 2110

Alfa AF: 0.0464 Hom.: 95

Bravo AF: 0.0489

Asia WGS AF: 0.0260 AC: 92 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.74
DANN	Benign	0.61
PhyloP100		-0.0070
Mutation Taster		=100/0	polymorphism

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: rs10096683; hg19: chr8-14162203;