rs2036819

Variant names:

• chr8-14729084-G-C
• rs2036819
• NM_139167.4:c.40-174158C>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.40-174158C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.381 in 151,960 control chromosomes in the GnomAD database, including 12,884 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 0.38 (12884 hom., cov: 32)
• Consequence: SGCZ NM_139167.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.508
• Publications: 0 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]

ENSG00000305769 (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 (AFR) allele frequency at 95% confidence interval = 0.609 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SGCZ	NM_139167.4	c.40-174158C>G		intron_variant	Intron 1 of 7	ENST00000382080.6	NP_631906.2
SGCZ	NM_001322879.2	c.40-174158C>G		intron_variant	Intron 1 of 6		NP_001309808.1
SGCZ	NM_001322880.2	c.40-174158C>G		intron_variant	Intron 1 of 6		NP_001309809.1
SGCZ	NM_001322881.2	c.-89-174158C>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.40-174158C>G		intron_variant	Intron 1 of 7	5	NM_139167.4	ENSP00000371512.1
ENSG00000305769	ENST00000812855.1	n.235+5738G>C		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.380 AC: 57747 AN: 151842 Hom.: 12848 Cov.: 32

Gnomad AFR AF: 0.615

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.419

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.439

Gnomad SAS AF: 0.338

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.252

Gnomad OTH AF: 0.361

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

GnomAD4 genome AF: 0.381 AC: 57839 AN: 151960 Hom.: 12884 Cov.: 32 AF XY: 0.382 AC XY: 28336 AN XY: 74260

African (AFR) AF: 0.615 AC: 25491 AN: 41434

American (AMR) AF: 0.420 AC: 6414 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.285 AC: 989 AN: 3466

East Asian (EAS) AF: 0.439 AC: 2256 AN: 5144

South Asian (SAS) AF: 0.338 AC: 1625 AN: 4814

European-Finnish (FIN) AF: 0.272 AC: 2871 AN: 10560

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.252 AC: 17124 AN: 67952

Other (OTH) AF: 0.362 AC: 764 AN: 2112

Alfa AF: 0.312 Hom.: 1129

Bravo AF: 0.401

Asia WGS AF: 0.396 AC: 1379 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	0.85
DANN	Benign	0.26
PhyloP100		-0.51
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: rs2036819; hg19: chr8-14586593;