8-14299941-G-A

Variant names:

• chr8-14299941-G-A
• rs1319570
• NM_139167.4:c.336+24162C>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.336+24162C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.945 in 151,972 control chromosomes in the GnomAD database, including 68,248 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 0.94 (68248 hom., cov: 31)
• Consequence: SGCZ NM_139167.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.864
• 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=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.99 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SGCZ	NM_139167.4	c.336+24162C>T		intron_variant	Intron 3 of 7	ENST00000382080.6	NP_631906.2
SGCZ	NM_001322879.2	c.235-62262C>T		intron_variant	Intron 2 of 6		NP_001309808.1
SGCZ	NM_001322880.2	c.336+24162C>T		intron_variant	Intron 3 of 6		NP_001309809.1
SGCZ	NM_001322881.2	c.114+24162C>T		intron_variant	Intron 3 of 6		NP_001309810.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SGCZ	ENST00000382080.6	c.336+24162C>T		intron_variant	Intron 3 of 7	5	NM_139167.4	ENSP00000371512.1
SGCZ	ENST00000421524.6	c.196-62262C>T		intron_variant	Intron 1 of 5	1		ENSP00000405224.2

Frequencies

GnomAD3 genomes AF: 0.945 AC: 143477 AN: 151852 Hom.: 68219 Cov.: 31

Gnomad AFR AF: 0.827

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.965

Gnomad ASJ AF: 0.968

Gnomad EAS AF: 0.990

Gnomad SAS AF: 0.969

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.953

Gnomad NFE AF: 0.996

Gnomad OTH AF: 0.955

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

GnomAD4 genome AF: 0.945 AC: 143560 AN: 151972 Hom.: 68248 Cov.: 31 AF XY: 0.946 AC XY: 70285 AN XY: 74272

African (AFR) AF: 0.826 AC: 34256 AN: 41454

American (AMR) AF: 0.965 AC: 14694 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.968 AC: 3358 AN: 3468

East Asian (EAS) AF: 0.990 AC: 5111 AN: 5164

South Asian (SAS) AF: 0.969 AC: 4678 AN: 4828

European-Finnish (FIN) AF: 1.00 AC: 10603 AN: 10604

Middle Eastern (MID) AF: 0.952 AC: 280 AN: 294

European-Non Finnish (NFE) AF: 0.996 AC: 67651 AN: 67910

Other (OTH) AF: 0.956 AC: 2017 AN: 2110

Alfa AF: 0.962 Hom.: 9291

Bravo AF: 0.937

Asia WGS AF: 0.953 AC: 3307 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.74
DANN	Benign	0.47
PhyloP100		-0.86
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: rs1319570; hg19: chr8-14157450;