chr8-14256307-G-A

Variant names:

• chr8-14256307-G-A
• rs9886428
• NM_139167.4:c.337-18628C>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.337-18628C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 151,870 control chromosomes in the GnomAD database, including 12,557 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 0.38 (12557 hom., cov: 32)
• Consequence: SGCZ NM_139167.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.236
• Publications: 4 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=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SGCZ	NM_139167.4	c.337-18628C>T		intron_variant	Intron 3 of 7	ENST00000382080.6	NP_631906.2
SGCZ	NM_001322879.2	c.235-18628C>T		intron_variant	Intron 2 of 6		NP_001309808.1
SGCZ	NM_001322880.2	c.337-18628C>T		intron_variant	Intron 3 of 6		NP_001309809.1
SGCZ	NM_001322881.2	c.115-18628C>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.337-18628C>T		intron_variant	Intron 3 of 7	5	NM_139167.4	ENSP00000371512.1
SGCZ	ENST00000421524.6	c.196-18628C>T		intron_variant	Intron 1 of 5	1		ENSP00000405224.2

Frequencies

GnomAD3 genomes AF: 0.384 AC: 58230 AN: 151752 Hom.: 12559 Cov.: 32

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.543

Gnomad AMR AF: 0.357

Gnomad ASJ AF: 0.510

Gnomad EAS AF: 0.266

Gnomad SAS AF: 0.233

Gnomad FIN AF: 0.423

Gnomad MID AF: 0.410

Gnomad NFE AF: 0.501

Gnomad OTH AF: 0.417

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

GnomAD4 genome AF: 0.384 AC: 58249 AN: 151870 Hom.: 12557 Cov.: 32 AF XY: 0.374 AC XY: 27778 AN XY: 74204

African (AFR) AF: 0.207 AC: 8591 AN: 41436

American (AMR) AF: 0.357 AC: 5437 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.510 AC: 1766 AN: 3466

East Asian (EAS) AF: 0.266 AC: 1373 AN: 5154

South Asian (SAS) AF: 0.232 AC: 1117 AN: 4814

European-Finnish (FIN) AF: 0.423 AC: 4461 AN: 10544

Middle Eastern (MID) AF: 0.421 AC: 122 AN: 290

European-Non Finnish (NFE) AF: 0.501 AC: 34015 AN: 67904

Other (OTH) AF: 0.413 AC: 873 AN: 2112

Alfa AF: 0.468 Hom.: 74726

Bravo AF: 0.377

Asia WGS AF: 0.229 AC: 796 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.4
DANN	Benign	0.16
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: rs9886428; hg19: chr8-14113816;