8-14850621-A-G

Position:

• chr8-14850621-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_139167.4(SGCZ):​c.40-295695T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0155 in 152,318 control chromosomes in the GnomAD database, including 42 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 0.016 (42 hom., cov: 32)
• Consequence: SGCZ NM_139167.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0280

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=-1.01).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0155 (2363/152318) while in subpopulation AFR AF= 0.0402 (1669/41564). AF 95% confidence interval is 0.0386. There are 42 homozygotes in gnomad4. There are 1148 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 42 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SGCZ	NM_139167.4	c.40-295695T>C		intron_variant		ENST00000382080.6	NP_631906.2
SGCZ	NM_001322879.2	c.40-295695T>C		intron_variant			NP_001309808.1
SGCZ	NM_001322880.2	c.40-295695T>C		intron_variant			NP_001309809.1
SGCZ	NM_001322881.2	c.-89-295695T>C		intron_variant			NP_001309810.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SGCZ	ENST00000382080.6	c.40-295695T>C		intron_variant		5	NM_139167.4	ENSP00000371512.1

Frequencies

GnomAD3 genomes AF: 0.0155 AC: 2354 AN: 152200 Hom.: 41 Cov.: 32

Gnomad AFR AF: 0.0402

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00563

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.0170

Gnomad FIN AF: 0.00490

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00620

Gnomad OTH AF: 0.0119

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

GnomAD4 genome AF: 0.0155 AC: 2363 AN: 152318 Hom.: 42 Cov.: 32 AF XY: 0.0154 AC XY: 1148 AN XY: 74488

Gnomad4 AFR AF: 0.0402

Gnomad4 AMR AF: 0.00562

Gnomad4 ASJ AF: 0.00259

Gnomad4 EAS AF: 0.00232

Gnomad4 SAS AF: 0.0178

Gnomad4 FIN AF: 0.00490

Gnomad4 NFE AF: 0.00620

Gnomad4 OTH AF: 0.0118

Alfa AF: 0.0142 Hom.: 5

Bravo AF: 0.0160

Asia WGS AF: 0.0220 AC: 80 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.5
DANN	Benign	0.51

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: rs10503516; hg19: chr8-14708130;