8-117013406-T-G

Variant names:

• chr8-117013406-T-G
• rs3019885
• ENST00000521243.5:c.-107+62287T>G

Variant summary

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

The ENST00000521243.5(SLC30A8):​c.-107+62287T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 152,136 control chromosomes in the GnomAD database, including 11,181 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 0.36 (11181 hom., cov: 32)
• Consequence: SLC30A8 ENST00000521243.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.556
• Publications: 45 publications found

Genes affected

SLC30A8 (HGNC:20303): (solute carrier family 30 member 8) The protein encoded by this gene is a zinc efflux transporter involved in the accumulation of zinc in intracellular vesicles. This gene is expressed at a high level only in the pancreas, particularly in islets of Langerhans. The encoded protein colocalizes with insulin in the secretory pathway granules of the insulin-secreting INS-1 cells. Allelic variants of this gene exist that confer susceptibility to diabetes mellitus, noninsulin-dependent (NIDDM). Several transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Mar 2010]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.484 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC30A8	NM_001172811.2	c.-107+62287T>G		intron_variant	Intron 2 of 9		NP_001166282.1
SLC30A8	NM_001172813.2	c.-274+6293T>G		intron_variant	Intron 2 of 10		NP_001166284.1
SLC30A8	NM_001172815.3	c.-265-25813T>G		intron_variant	Intron 1 of 10		NP_001166286.1
SLC30A8	XM_024447083.2	c.-107+62287T>G		intron_variant	Intron 1 of 8		XP_024302851.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC30A8	ENST00000521243.5	c.-107+62287T>G		intron_variant	Intron 2 of 9	1		ENSP00000428545.1
SLC30A8	ENST00000427715.2	c.-265-25813T>G		intron_variant	Intron 1 of 10	2		ENSP00000407505.2
SLC30A8	ENST00000524274.5	c.-107+62287T>G		intron_variant	Intron 2 of 4	4		ENSP00000427760.1
SLC30A8	ENST00000521035.5	n.294+6293T>G		intron_variant	Intron 2 of 4	4

Frequencies

GnomAD3 genomes AF: 0.360 AC: 54707 AN: 152016 Hom.: 11171 Cov.: 32

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.385

Gnomad AMR AF: 0.493

Gnomad ASJ AF: 0.355

Gnomad EAS AF: 0.276

Gnomad SAS AF: 0.487

Gnomad FIN AF: 0.328

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.450

Gnomad OTH AF: 0.400

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

GnomAD4 genome AF: 0.360 AC: 54739 AN: 152136 Hom.: 11181 Cov.: 32 AF XY: 0.361 AC XY: 26860 AN XY: 74376

African (AFR) AF: 0.164 AC: 6795 AN: 41542

American (AMR) AF: 0.493 AC: 7527 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.355 AC: 1232 AN: 3472

East Asian (EAS) AF: 0.275 AC: 1425 AN: 5180

South Asian (SAS) AF: 0.489 AC: 2360 AN: 4822

European-Finnish (FIN) AF: 0.328 AC: 3469 AN: 10580

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.450 AC: 30611 AN: 67962

Other (OTH) AF: 0.395 AC: 834 AN: 2114

Alfa AF: 0.420 Hom.: 53876

Bravo AF: 0.361

Asia WGS AF: 0.342 AC: 1189 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.1
DANN	Benign	0.77
PhyloP100		0.56
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3019885; hg19: chr8-118025645;