8-15220912-T-G

Variant names:

• chr8-15220912-T-G
• rs268346
• NM_139167.4:c.39+16673A>C

Variant summary

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

The NM_139167.4(SGCZ):​c.39+16673A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.885 in 152,066 control chromosomes in the GnomAD database, including 59,738 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 0.89 (59738 hom., cov: 30)
• Consequence: SGCZ NM_139167.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.799
• 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=-1.03).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.9 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.39+16673A>C		intron	N/A	NP_631906.2
	SGCZ	NM_001322879.2		c.39+16673A>C		intron	N/A	NP_001309808.1
	SGCZ	NM_001322880.2		c.39+16673A>C		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.39+16673A>C		intron	N/A	ENSP00000371512.1

Frequencies

GnomAD3 genomes AF: 0.885 AC: 134541 AN: 151950 Hom.: 59700 Cov.: 30

Gnomad AFR AF: 0.852

Gnomad AMI AF: 0.978

Gnomad AMR AF: 0.856

Gnomad ASJ AF: 0.881

Gnomad EAS AF: 0.794

Gnomad SAS AF: 0.894

Gnomad FIN AF: 0.957

Gnomad MID AF: 0.886

Gnomad NFE AF: 0.906

Gnomad OTH AF: 0.893

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

GnomAD4 genome AF: 0.885 AC: 134638 AN: 152066 Hom.: 59738 Cov.: 30 AF XY: 0.888 AC XY: 66054 AN XY: 74344

African (AFR) AF: 0.851 AC: 35313 AN: 41476

American (AMR) AF: 0.856 AC: 13078 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.881 AC: 3058 AN: 3472

East Asian (EAS) AF: 0.794 AC: 4060 AN: 5114

South Asian (SAS) AF: 0.894 AC: 4296 AN: 4806

European-Finnish (FIN) AF: 0.957 AC: 10147 AN: 10600

Middle Eastern (MID) AF: 0.888 AC: 261 AN: 294

European-Non Finnish (NFE) AF: 0.906 AC: 61652 AN: 68016

Other (OTH) AF: 0.894 AC: 1881 AN: 2104

Alfa AF: 0.900 Hom.: 2976

Bravo AF: 0.874

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.87
DANN	Benign	0.38
PhyloP100		-0.80
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: rs268346; hg19: chr8-15078421;