8-14424873-A-C

Position:

• chr8-14424873-A-C

Variant summary

Our verdict is Benign. Variant got -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

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=-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/exons	MANE	Protein	UniProt
SGCZ	NM_139167.4	c.235-100669T>G		intron_variant		ENST00000382080.6	NP_631906.2
SGCZ	NM_001322879.2	c.234+129859T>G		intron_variant			NP_001309808.1
SGCZ	NM_001322880.2	c.235-100669T>G		intron_variant			NP_001309809.1
SGCZ	NM_001322881.2	c.13-100669T>G		intron_variant			NP_001309810.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SGCZ	ENST00000382080.6	c.235-100669T>G		intron_variant		5	NM_139167.4	ENSP00000371512	P1
SGCZ	ENST00000421524.6	c.195+129859T>G		intron_variant		1		ENSP00000405224

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

Gnomad4 AFR AF: 0.0809

Gnomad4 AMR AF: 0.209

Gnomad4 ASJ AF: 0.313

Gnomad4 EAS AF: 0.0641

Gnomad4 SAS AF: 0.125

Gnomad4 FIN AF: 0.235

Gnomad4 NFE AF: 0.288

Gnomad4 OTH AF: 0.221

Alfa AF: 0.264 Hom.: 6512

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

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: rs10503497; hg19: chr8-14282382;