NM_139167.4:c.39+173119T>A

Variant names:

• chr8-15064466-A-T
• rs7464441
• NM_139167.4:c.39+173119T>A

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+173119T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.87 in 151,240 control chromosomes in the GnomAD database, including 57,667 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 0.87 (57667 hom., cov: 27)
• Consequence: SGCZ NM_139167.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.978
• Publications: 3 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]

ENSG00000301307 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SGCZ	NM_139167.4	c.39+173119T>A		intron_variant	Intron 1 of 7	ENST00000382080.6	NP_631906.2
SGCZ	NM_001322879.2	c.39+173119T>A		intron_variant	Intron 1 of 6		NP_001309808.1
SGCZ	NM_001322880.2	c.39+173119T>A		intron_variant	Intron 1 of 6		NP_001309809.1
SGCZ	NM_001322881.2	c.-90+173119T>A		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+173119T>A		intron_variant	Intron 1 of 7	5	NM_139167.4	ENSP00000371512.1
ENSG00000301307	ENST00000777843.1	n.90-13272T>A		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.870 AC: 131546 AN: 151128 Hom.: 57623 Cov.: 27

Gnomad AFR AF: 0.768

Gnomad AMI AF: 0.950

Gnomad AMR AF: 0.929

Gnomad ASJ AF: 0.941

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.948

Gnomad FIN AF: 0.917

Gnomad MID AF: 0.864

Gnomad NFE AF: 0.891

Gnomad OTH AF: 0.885

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

GnomAD4 genome AF: 0.870 AC: 131646 AN: 151240 Hom.: 57667 Cov.: 27 AF XY: 0.875 AC XY: 64638 AN XY: 73846

African (AFR) AF: 0.768 AC: 31409 AN: 40880

American (AMR) AF: 0.930 AC: 14171 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.941 AC: 3265 AN: 3470

East Asian (EAS) AF: 0.997 AC: 5112 AN: 5128

South Asian (SAS) AF: 0.948 AC: 4553 AN: 4804

European-Finnish (FIN) AF: 0.917 AC: 9594 AN: 10464

Middle Eastern (MID) AF: 0.867 AC: 255 AN: 294

European-Non Finnish (NFE) AF: 0.891 AC: 60564 AN: 67948

Other (OTH) AF: 0.886 AC: 1857 AN: 2096

Alfa AF: 0.875 Hom.: 7261

Bravo AF: 0.865

Asia WGS AF: 0.959 AC: 3331 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.7
DANN	Benign	0.50
PhyloP100		-0.98
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: rs7464441; hg19: chr8-14921975;