NM_139167.4:c.40-54493A>G

Variant names:

• chr8-14609419-T-C
• rs4831616
• NM_139167.4:c.40-54493A>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.40-54493A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.78 in 152,022 control chromosomes in the GnomAD database, including 46,700 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 0.78 (46700 hom., cov: 32)
• Consequence: SGCZ NM_139167.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.30
• Publications: 2 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.823 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGCZ	NM_139167.4	MANE Select	c.40-54493A>G		intron	N/A	NP_631906.2	Q96LD1-2
	SGCZ	NM_001322879.2		c.40-54493A>G		intron	N/A	NP_001309808.1
	SGCZ	NM_001322880.2		c.40-54493A>G		intron	N/A	NP_001309809.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SGCZ	ENST00000382080.6	TSL:5 MANE Select	c.40-54493A>G		intron	N/A	ENSP00000371512.1	Q96LD1-2

Frequencies

GnomAD3 genomes AF: 0.781 AC: 118583 AN: 151904 Hom.: 46683 Cov.: 32

Gnomad AFR AF: 0.677

Gnomad AMI AF: 0.848

Gnomad AMR AF: 0.805

Gnomad ASJ AF: 0.843

Gnomad EAS AF: 0.796

Gnomad SAS AF: 0.670

Gnomad FIN AF: 0.863

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.829

Gnomad OTH AF: 0.778

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

GnomAD4 genome AF: 0.780 AC: 118646 AN: 152022 Hom.: 46700 Cov.: 32 AF XY: 0.782 AC XY: 58075 AN XY: 74308

African (AFR) AF: 0.676 AC: 28023 AN: 41430

American (AMR) AF: 0.806 AC: 12305 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.843 AC: 2924 AN: 3470

East Asian (EAS) AF: 0.795 AC: 4110 AN: 5168

South Asian (SAS) AF: 0.669 AC: 3221 AN: 4816

European-Finnish (FIN) AF: 0.863 AC: 9127 AN: 10574

Middle Eastern (MID) AF: 0.703 AC: 204 AN: 290

European-Non Finnish (NFE) AF: 0.829 AC: 56331 AN: 67984

Other (OTH) AF: 0.771 AC: 1629 AN: 2112

Alfa AF: 0.800 Hom.: 34129

Bravo AF: 0.775

Asia WGS AF: 0.688 AC: 2392 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.5
DANN	Benign	0.84
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs4831616; hg19: chr8-14466928;