NM_139167.4:c.40-44496C>A

Variant names:

• chr8-14599422-G-T
• rs6987209
• NM_139167.4:c.40-44496C>A

Variant summary

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

The NM_139167.4(SGCZ):​c.40-44496C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0531 in 152,176 control chromosomes in the GnomAD database, including 250 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 0.053 (250 hom., cov: 32)
• Consequence: SGCZ NM_139167.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.661
• 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.134 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SGCZ	NM_139167.4	c.40-44496C>A		intron_variant	Intron 1 of 7	ENST00000382080.6	NP_631906.2
SGCZ	NM_001322879.2	c.40-44496C>A		intron_variant	Intron 1 of 6		NP_001309808.1
SGCZ	NM_001322880.2	c.40-44496C>A		intron_variant	Intron 1 of 6		NP_001309809.1
SGCZ	NM_001322881.2	c.-89-44496C>A		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.40-44496C>A		intron_variant	Intron 1 of 7	5	NM_139167.4	ENSP00000371512.1

Frequencies

GnomAD3 genomes AF: 0.0531 AC: 8072 AN: 152058 Hom.: 248 Cov.: 32

Gnomad AFR AF: 0.0531

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0533

Gnomad ASJ AF: 0.0473

Gnomad EAS AF: 0.0862

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.0452

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0464

Gnomad OTH AF: 0.0536

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

GnomAD4 genome AF: 0.0531 AC: 8079 AN: 152176 Hom.: 250 Cov.: 32 AF XY: 0.0546 AC XY: 4060 AN XY: 74410

African (AFR) AF: 0.0531 AC: 2206 AN: 41520

American (AMR) AF: 0.0531 AC: 812 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0473 AC: 164 AN: 3468

East Asian (EAS) AF: 0.0864 AC: 446 AN: 5164

South Asian (SAS) AF: 0.142 AC: 686 AN: 4820

European-Finnish (FIN) AF: 0.0452 AC: 479 AN: 10600

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0464 AC: 3158 AN: 68006

Other (OTH) AF: 0.0531 AC: 112 AN: 2110

Alfa AF: 0.0378 Hom.: 47

Bravo AF: 0.0527

Asia WGS AF: 0.119 AC: 413 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.91
DANN	Benign	0.42
PhyloP100		-0.66
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: rs6987209; hg19: chr8-14456931;