rs2466295

Variant names:

• chr8-117172802-C-T
• rs2466295
• NM_173851.3:c.*121C>T

Variant summary

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

The NM_173851.3(SLC30A8):​c.*121C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.621 in 1,127,406 control chromosomes in the GnomAD database, including 223,955 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 0.55 (24918 hom., cov: 33)
  • Exomes 𝑓: 0.63 (199037 hom.)
• Consequence: SLC30A8 NM_173851.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0820
• Publications: 21 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]

LOC105375716 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.799 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC30A8	NM_173851.3	c.*121C>T		3_prime_UTR_variant	Exon 8 of 8	ENST00000456015.7	NP_776250.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC30A8	ENST00000456015.7	c.*121C>T		3_prime_UTR_variant	Exon 8 of 8	1	NM_173851.3	ENSP00000415011.2
SLC30A8	ENST00000519688.5	c.*121C>T		3_prime_UTR_variant	Exon 9 of 9	1		ENSP00000431069.1
SLC30A8	ENST00000427715.2	c.*121C>T		3_prime_UTR_variant	Exon 11 of 11	2		ENSP00000407505.2
SLC30A8	ENST00000521243.5	c.*121C>T		downstream_gene_variant		1		ENSP00000428545.1

Frequencies

GnomAD3 genomes AF: 0.546 AC: 82950 AN: 151910 Hom.: 24904 Cov.: 33

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.656

Gnomad AMR AF: 0.638

Gnomad ASJ AF: 0.587

Gnomad EAS AF: 0.819

Gnomad SAS AF: 0.634

Gnomad FIN AF: 0.728

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.633

Gnomad OTH AF: 0.552

GnomAD4 exome AF: 0.633 AC: 617344 AN: 975378 Hom.: 199037 Cov.: 13 AF XY: 0.632 AC XY: 313810 AN XY: 496328

African (AFR) AF: 0.262 AC: 5949 AN: 22690

American (AMR) AF: 0.684 AC: 20116 AN: 29394

Ashkenazi Jewish (ASJ) AF: 0.591 AC: 10722 AN: 18152

East Asian (EAS) AF: 0.832 AC: 30872 AN: 37114

South Asian (SAS) AF: 0.609 AC: 38318 AN: 62868

European-Finnish (FIN) AF: 0.711 AC: 33298 AN: 46824

Middle Eastern (MID) AF: 0.568 AC: 2616 AN: 4608

European-Non Finnish (NFE) AF: 0.632 AC: 448703 AN: 709936

Other (OTH) AF: 0.611 AC: 26750 AN: 43792

GnomAD4 genome AF: 0.546 AC: 82991 AN: 152028 Hom.: 24918 Cov.: 33 AF XY: 0.555 AC XY: 41236 AN XY: 74308

African (AFR) AF: 0.272 AC: 11288 AN: 41482

American (AMR) AF: 0.639 AC: 9747 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.587 AC: 2036 AN: 3466

East Asian (EAS) AF: 0.819 AC: 4222 AN: 5154

South Asian (SAS) AF: 0.633 AC: 3050 AN: 4820

European-Finnish (FIN) AF: 0.728 AC: 7695 AN: 10570

Middle Eastern (MID) AF: 0.644 AC: 188 AN: 292

European-Non Finnish (NFE) AF: 0.633 AC: 42998 AN: 67962

Other (OTH) AF: 0.553 AC: 1169 AN: 2114

Alfa AF: 0.573 Hom.: 41985

Bravo AF: 0.530

Asia WGS AF: 0.645 AC: 2241 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.5
DANN	Benign	0.37
PhyloP100		0.082
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: rs2466295; hg19: chr8-118185041; COSMIC: COSV69975536; COSMIC: COSV69975536;