8-14659785-T-C

Variant names:

• chr8-14659785-T-C
• rs11203649
• NM_139167.4:c.40-104859A>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.40-104859A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.716 in 152,096 control chromosomes in the GnomAD database, including 40,296 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 0.72 (40296 hom., cov: 32)
• Consequence: SGCZ NM_139167.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.732
• Publications: 5 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 (AFR) allele frequency at 95% confidence interval = 0.883 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SGCZ	NM_139167.4	c.40-104859A>G		intron_variant	Intron 1 of 7	ENST00000382080.6	NP_631906.2
SGCZ	NM_001322879.2	c.40-104859A>G		intron_variant	Intron 1 of 6		NP_001309808.1
SGCZ	NM_001322880.2	c.40-104859A>G		intron_variant	Intron 1 of 6		NP_001309809.1
SGCZ	NM_001322881.2	c.-89-104859A>G		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.40-104859A>G		intron_variant	Intron 1 of 7	5	NM_139167.4	ENSP00000371512.1

Frequencies

GnomAD3 genomes AF: 0.716 AC: 108756 AN: 151978 Hom.: 40223 Cov.: 32

Gnomad AFR AF: 0.890

Gnomad AMI AF: 0.418

Gnomad AMR AF: 0.783

Gnomad ASJ AF: 0.715

Gnomad EAS AF: 0.830

Gnomad SAS AF: 0.689

Gnomad FIN AF: 0.637

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.603

Gnomad OTH AF: 0.729

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

GnomAD4 genome AF: 0.716 AC: 108889 AN: 152096 Hom.: 40296 Cov.: 32 AF XY: 0.718 AC XY: 53352 AN XY: 74326

African (AFR) AF: 0.890 AC: 36968 AN: 41520

American (AMR) AF: 0.783 AC: 11965 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.715 AC: 2480 AN: 3470

East Asian (EAS) AF: 0.830 AC: 4288 AN: 5168

South Asian (SAS) AF: 0.690 AC: 3320 AN: 4814

European-Finnish (FIN) AF: 0.637 AC: 6727 AN: 10556

Middle Eastern (MID) AF: 0.714 AC: 210 AN: 294

European-Non Finnish (NFE) AF: 0.603 AC: 41005 AN: 67968

Other (OTH) AF: 0.731 AC: 1545 AN: 2114

Alfa AF: 0.650 Hom.: 39904

Bravo AF: 0.740

Asia WGS AF: 0.768 AC: 2670 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.99
DANN	Benign	0.78
PhyloP100		-0.73
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: rs11203649; hg19: chr8-14517294;