NM_139167.4:c.39+63527C>T

Variant names:

• chr8-15174058-G-A
• rs268387
• NM_139167.4:c.39+63527C>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.39+63527C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.53 in 151,890 control chromosomes in the GnomAD database, including 21,598 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 0.53 (21598 hom., cov: 32)
• Consequence: SGCZ NM_139167.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.82
• Publications: 8 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=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.554 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SGCZ	NM_139167.4	c.39+63527C>T		intron_variant	Intron 1 of 7	ENST00000382080.6	NP_631906.2
SGCZ	NM_001322879.2	c.39+63527C>T		intron_variant	Intron 1 of 6		NP_001309808.1
SGCZ	NM_001322880.2	c.39+63527C>T		intron_variant	Intron 1 of 6		NP_001309809.1
SGCZ	NM_001322881.2	c.-90+63527C>T		intron_variant	Intron 1 of 6		NP_001309810.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SGCZ	ENST00000382080.6	c.39+63527C>T		intron_variant	Intron 1 of 7	5	NM_139167.4	ENSP00000371512.1

Frequencies

GnomAD3 genomes AF: 0.530 AC: 80507 AN: 151772 Hom.: 21577 Cov.: 32

Gnomad AFR AF: 0.508

Gnomad AMI AF: 0.348

Gnomad AMR AF: 0.452

Gnomad ASJ AF: 0.576

Gnomad EAS AF: 0.351

Gnomad SAS AF: 0.458

Gnomad FIN AF: 0.683

Gnomad MID AF: 0.410

Gnomad NFE AF: 0.558

Gnomad OTH AF: 0.501

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

GnomAD4 genome AF: 0.530 AC: 80575 AN: 151890 Hom.: 21598 Cov.: 32 AF XY: 0.531 AC XY: 39380 AN XY: 74208

African (AFR) AF: 0.508 AC: 21029 AN: 41384

American (AMR) AF: 0.452 AC: 6893 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.576 AC: 1999 AN: 3470

East Asian (EAS) AF: 0.351 AC: 1815 AN: 5168

South Asian (SAS) AF: 0.457 AC: 2205 AN: 4822

European-Finnish (FIN) AF: 0.683 AC: 7200 AN: 10542

Middle Eastern (MID) AF: 0.407 AC: 118 AN: 290

European-Non Finnish (NFE) AF: 0.558 AC: 37932 AN: 67938

Other (OTH) AF: 0.506 AC: 1069 AN: 2114

Alfa AF: 0.542 Hom.: 12392

Bravo AF: 0.513

Asia WGS AF: 0.436 AC: 1520 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.0080
DANN	Benign	0.65
PhyloP100		-1.8
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: rs268387; hg19: chr8-15031567;