rs11994326

chr8-14536716-A-Gchr8-14536716-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_139167.4(SGCZ):c.234+18016T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0942 in 151,894 control chromosomes in the GnomAD database, including 1,139 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 0.094 (1139 hom., cov: 32)
• Consequence: SGCZ NM_139167.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.835

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SGCZ	NM_139167.4	c.234+18016T>C		intron_variant		ENST00000382080.6
SGCZ	NM_001322879.2	c.234+18016T>C		intron_variant
SGCZ	NM_001322880.2	c.234+18016T>C		intron_variant
SGCZ	NM_001322881.2	c.12+18110T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SGCZ	ENST00000382080.6	c.234+18016T>C		intron_variant		5	NM_139167.4	P1
SGCZ	ENST00000421524.6	c.195+18016T>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.0942 AC: 14294 AN: 151774 Hom.: 1137 Cov.: 32

Gnomad AFR AF: 0.215

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0642

Gnomad ASJ AF: 0.0401

Gnomad EAS AF: 0.0955

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.0515

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0374

Gnomad OTH AF: 0.0648

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

GnomAD4 genome AF: 0.0942 AC: 14301 AN: 151894 Hom.: 1139 Cov.: 32 AF XY: 0.0943 AC XY: 7000 AN XY: 74232

Gnomad4 AFR AF: 0.214

Gnomad4 AMR AF: 0.0642

Gnomad4 ASJ AF: 0.0401

Gnomad4 EAS AF: 0.0959

Gnomad4 SAS AF: 0.117

Gnomad4 FIN AF: 0.0515

Gnomad4 NFE AF: 0.0374

Gnomad4 OTH AF: 0.0637

Alfa AF: 0.0446 Hom.: 136

Bravo AF: 0.0997

Asia WGS AF: 0.115 AC: 398 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	0.85
Dann	Benign	0.69

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

Publications

LitVar

Other links and lift over

dbSNP: rs11994326; hg19: chr8-14394225;