chr8-117152033-C-T

Variant names:

• chr8-117152033-C-T
• rs62510556
• NM_173851.3:c.272-911C>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.272-911C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 152,082 control chromosomes in the GnomAD database, including 2,258 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 0.16 (2258 hom., cov: 32)
• Consequence: SLC30A8 NM_173851.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.777
• Publications: 2 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]

SLC30A8 Gene-Disease associations (from GenCC):

• type 2 diabetes mellitus

  Inheritance: AD Classification: LIMITED Submitted by: PanelApp Australia

LOC105375716 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.259 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173851.3. 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
	SLC30A8	NM_173851.3	MANE Select	c.272-911C>T		intron	N/A	NP_776250.2	Q8IWU4-1
	SLC30A8	NM_001172811.2		c.125-911C>T		intron	N/A	NP_001166282.1	Q8IWU4-2
	SLC30A8	NM_001172813.2		c.125-911C>T		intron	N/A	NP_001166284.1	Q8IWU4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC30A8	ENST00000456015.7	TSL:1 MANE Select	c.272-911C>T		intron	N/A	ENSP00000415011.2	Q8IWU4-1
	SLC30A8	ENST00000519688.5	TSL:1	c.125-911C>T		intron	N/A	ENSP00000431069.1	Q8IWU4-2
	SLC30A8	ENST00000521243.5	TSL:1	c.125-911C>T		intron	N/A	ENSP00000428545.1	Q8IWU4-2

Frequencies

GnomAD3 genomes AF: 0.158 AC: 24083 AN: 151964 Hom.: 2254 Cov.: 32

Gnomad AFR AF: 0.0657

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.270

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.155

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

GnomAD4 genome AF: 0.158 AC: 24093 AN: 152082 Hom.: 2258 Cov.: 32 AF XY: 0.156 AC XY: 11582 AN XY: 74318

African (AFR) AF: 0.0657 AC: 2728 AN: 41498

American (AMR) AF: 0.138 AC: 2111 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 646 AN: 3468

East Asian (EAS) AF: 0.270 AC: 1398 AN: 5170

South Asian (SAS) AF: 0.154 AC: 741 AN: 4812

European-Finnish (FIN) AF: 0.160 AC: 1686 AN: 10552

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.210 AC: 14263 AN: 67994

Other (OTH) AF: 0.156 AC: 330 AN: 2110

Alfa AF: 0.170 Hom.: 326

Bravo AF: 0.152

Asia WGS AF: 0.218 AC: 754 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	0.39
DANN	Benign	0.76
PhyloP100		-0.78
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: rs62510556; hg19: chr8-118164272; COSMIC: COSV69975349; COSMIC: COSV69975349;