8-117172544-C-T

Position:

chr8-117172544-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_173851.3(SLC30A8):c.973C>T(p.Arg325Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 1,613,268 control chromosomes in the GnomAD database, including 73,380 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign,risk factor (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R325Q) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.25 ( 5580 hom., cov: 33)

Exomes 𝑓: 0.30 ( 67800 hom. )

Consequence

SLC30A8
NM_173851.3 missense

Scores

Clinical Significance

Benign; risk factor no assertion criteria provided B:1O:1

Conservation

PhyloP100: -0.742

Variant links:

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 links:

LOC105375716 (HGNC:):

LOC105375716 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=9.0557337E-4).

BP6

Variant 8-117172544-C-T is Benign according to our data. Variant chr8-117172544-C-T is described in ClinVar as [Benign, risk_factor]. Clinvar id is 1000.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.435 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC30A8	NM_173851.3 linkuse as main transcript	c.973C>T	p.Arg325Trp	missense_variant	8/8	ENST00000456015.7	NP_776250.2	Q8IWU4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SLC30A8	ENST00000456015.7 linkuse as main transcript	c.973C>T	p.Arg325Trp	missense_variant	8/8	1	NM_173851.3	ENSP00000415011.2	Q8IWU4-1
SLC30A8	ENST00000519688.5 linkuse as main transcript	c.826C>T	p.Arg276Trp	missense_variant	9/9	1		ENSP00000431069.1	Q8IWU4-2
SLC30A8	ENST00000521243.5 linkuse as main transcript	c.826C>T	p.Arg276Trp	missense_variant	10/10	1		ENSP00000428545.1	Q8IWU4-2
SLC30A8	ENST00000427715.2 linkuse as main transcript	c.826C>T	p.Arg276Trp	missense_variant	11/11	2		ENSP00000407505.2	Q8IWU4-2

Frequencies

GnomAD3 genomes

AF:

0.248

AC:

37664

AN:

152022

Hom.:

5578

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0923

Gnomad AMI

AF:

0.168

Gnomad AMR

AF:

0.249

Gnomad ASJ

AF:

0.263

Gnomad EAS

AF:

0.451

Gnomad SAS

AF:

0.232

Gnomad FIN

AF:

0.400

Gnomad MID

AF:

0.231

Gnomad NFE

AF:

0.304

Gnomad OTH

AF:

0.254

GnomAD3 exomes

AF:

0.288

AC:

71769

AN:

249394

Hom.:

11185

AF XY:

0.287

AC XY:

38728

AN XY:

134924

show subpopulations

Gnomad AFR exome

AF:

0.0873

Gnomad AMR exome

AF:

0.257

Gnomad ASJ exome

AF:

0.261

Gnomad EAS exome

AF:

0.439

Gnomad SAS exome

AF:

0.230

Gnomad FIN exome

AF:

0.380

Gnomad NFE exome

AF:

0.302

Gnomad OTH exome

AF:

0.286

GnomAD4 exome

AF:

0.301

AC:

439230

AN:

1461128

Hom.:

67800

Cov.:

AF XY:

0.300

AC XY:

217715

AN XY:

726894

show subpopulations

Gnomad4 AFR exome

AF:

0.0809

Gnomad4 AMR exome

AF:

0.254

Gnomad4 ASJ exome

AF:

0.262

Gnomad4 EAS exome

AF:

0.424

Gnomad4 SAS exome

AF:

0.234

Gnomad4 FIN exome

AF:

0.378

Gnomad4 NFE exome

AF:

0.308

Gnomad4 OTH exome

AF:

0.289

GnomAD4 genome

AF:

0.248

AC:

37676

AN:

152140

Hom.:

5580

Cov.:

AF XY:

0.253

AC XY:

18802

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.0922

Gnomad4 AMR

AF:

0.249

Gnomad4 ASJ

AF:

0.263

Gnomad4 EAS

AF:

0.451

Gnomad4 SAS

AF:

0.232

Gnomad4 FIN

AF:

0.400

Gnomad4 NFE

AF:

0.304

Gnomad4 OTH

AF:

0.252

Alfa

AF:

0.288

Hom.:

16020

Bravo

AF:

0.234

TwinsUK

AF:

0.298

AC:

1104

ALSPAC

AF:

0.299

AC:

1151

ESP6500AA

AF:

0.0967

AC:

426

ESP6500EA

AF:

0.298

AC:

2564

ExAC

AF:

0.285

AC:

34581

Asia WGS

AF:

0.285

AC:

989

AN:

3476

EpiCase

AF:

0.297

EpiControl

AF:

0.287

ClinVar

Significance: Benign; risk factor

Submissions summary: Benign:1Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SLC30A8-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 21, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Diabetes mellitus type 2, susceptibility to

Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Jun 01, 2007

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.50

CADD

Benign

9.8

DANN

Uncertain

0.98

DEOGEN2

Benign

0.22

.;.;.;T

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.088

LIST_S2

Benign

0.24

.;T;.;T

MetaRNN

Benign

0.00091

T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.7

.;.;.;L

PrimateAI

Benign

0.17

PROVEAN

Benign

-1.9

N;N;N;N

REVEL

Benign

0.12

Sift

Benign

0.044

D;D;D;T

Sift4G

Uncertain

0.056

T;T;T;T

Polyphen

0.0020

.;.;.;B

Vest4

0.089

MPC

0.048

ClinPred

0.032

GERP RS

-1.8

Varity_R

0.095

gMVP

0.46

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over