NM_139167.4:c.425-4042C>G

Variant names:

• chr8-14168744-G-C
• rs1478025
• NM_139167.4:c.425-4042C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_139167.4(SGCZ):​c.425-4042C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0755 in 152,104 control chromosomes in the GnomAD database, including 511 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 0.075 (511 hom., cov: 32)
• Consequence: SGCZ NM_139167.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0800
• Publications: 1 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139167.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGCZ	NM_139167.4	MANE Select	c.425-4042C>G		intron	N/A	NP_631906.2
	SGCZ	NM_001322879.2		c.323-4042C>G		intron	N/A	NP_001309808.1
	SGCZ	NM_001322880.2		c.425-60509C>G		intron	N/A	NP_001309809.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGCZ	ENST00000382080.6	TSL:5 MANE Select	c.425-4042C>G		intron	N/A	ENSP00000371512.1
	SGCZ	ENST00000421524.6	TSL:1	c.284-4042C>G		intron	N/A	ENSP00000405224.2

Frequencies

GnomAD3 genomes AF: 0.0754 AC: 11465 AN: 151986 Hom.: 513 Cov.: 32

Gnomad AFR AF: 0.0515

Gnomad AMI AF: 0.0341

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.0804

Gnomad EAS AF: 0.0877

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.104

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0711

Gnomad OTH AF: 0.0785

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

GnomAD4 genome AF: 0.0755 AC: 11480 AN: 152104 Hom.: 511 Cov.: 32 AF XY: 0.0785 AC XY: 5839 AN XY: 74358

African (AFR) AF: 0.0516 AC: 2142 AN: 41494

American (AMR) AF: 0.122 AC: 1863 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.0804 AC: 279 AN: 3470

East Asian (EAS) AF: 0.0876 AC: 453 AN: 5174

South Asian (SAS) AF: 0.120 AC: 577 AN: 4808

European-Finnish (FIN) AF: 0.104 AC: 1106 AN: 10588

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.0711 AC: 4832 AN: 67996

Other (OTH) AF: 0.0777 AC: 164 AN: 2110

Alfa AF: 0.0257 Hom.: 21

Bravo AF: 0.0775

Asia WGS AF: 0.0960 AC: 332 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.4
DANN	Benign	0.55
PhyloP100		-0.080
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: rs1478025; hg19: chr8-14026253;