rs16889462

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_173851.3(SLC30A8):c.974G>A(p.Arg325Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00792 in 1,613,552 control chromosomes in the GnomAD database, including 567 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R325W) has been classified as Benign.

Frequency

Genomes: 𝑓 0.033 ( 248 hom., cov: 33)

Exomes 𝑓: 0.0053 ( 319 hom. )

Consequence

SLC30A8
NM_173851.3 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.0580

Publications

36 publications found

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 was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014527738).

BP6

Variant 8-117172545-G-A is Benign according to our data. Variant chr8-117172545-G-A is described in ClinVar as Benign. ClinVar VariationId is 3038448.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC30A8	NM_173851.3 link	c.974G>A	p.Arg325Gln	missense_variant	Exon 8 of 8	ENST00000456015.7	NP_776250.2	Q8IWU4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC30A8	ENST00000456015.7 link	c.974G>A	p.Arg325Gln	missense_variant	Exon 8 of 8	1	NM_173851.3	ENSP00000415011.2	Q8IWU4-1
SLC30A8	ENST00000519688.5 link	c.827G>A	p.Arg276Gln	missense_variant	Exon 9 of 9	1		ENSP00000431069.1	Q8IWU4-2
SLC30A8	ENST00000521243.5 link	c.827G>A	p.Arg276Gln	missense_variant	Exon 10 of 10	1		ENSP00000428545.1	Q8IWU4-2
SLC30A8	ENST00000427715.2 link	c.827G>A	p.Arg276Gln	missense_variant	Exon 11 of 11	2		ENSP00000407505.2	Q8IWU4-2

Frequencies

GnomAD3 genomes

AF:

0.0330

AC:

5017

AN:

152116

Hom.:

242

Cov.:

show subpopulations

Gnomad AFR

AF:

0.105

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0124

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.0722

Gnomad SAS

AF:

0.00414

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000632

Gnomad OTH

AF:

0.0248

GnomAD2 exomes

AF:

0.0145

AC:

3620

AN:

249532

AF XY:

0.0122

show subpopulations

Gnomad AFR exome

AF:

0.106

Gnomad AMR exome

AF:

0.00576

Gnomad ASJ exome

AF:

0.00199

Gnomad EAS exome

AF:

0.0798

Gnomad FIN exome

AF:

0.000277

Gnomad NFE exome

AF:

0.000679

Gnomad OTH exome

AF:

0.00605

GnomAD4 exome

AF:

0.00530

AC:

7743

AN:

1461318

Hom.:

319

Cov.:

AF XY:

0.00491

AC XY:

3568

AN XY:

726974

show subpopulations

African (AFR)

AF:

0.107

AC:

3562

AN:

33428

American (AMR)

AF:

0.00667

AC:

298

AN:

44680

Ashkenazi Jewish (ASJ)

AF:

0.00172

AC:

AN:

26112

East Asian (EAS)

AF:

0.0604

AC:

2397

AN:

39690

South Asian (SAS)

AF:

0.00306

AC:

264

AN:

86254

European-Finnish (FIN)

AF:

0.000225

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00660

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.000368

AC:

409

AN:

1111636

Other (OTH)

AF:

0.0119

AC:

718

AN:

60346

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

407

814

1222

1629

2036

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

160

320

480

640

800

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0331

AC:

5041

AN:

152234

Hom.:

248

Cov.:

AF XY:

0.0327

AC XY:

2431

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.105

AC:

4354

AN:

41532

American (AMR)

AF:

0.0124

AC:

189

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00259

AC:

AN:

3470

East Asian (EAS)

AF:

0.0721

AC:

372

AN:

5156

South Asian (SAS)

AF:

0.00394

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0000941

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000632

AC:

AN:

68012

Other (OTH)

AF:

0.0246

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

232

464

697

929

1161

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

168

224

280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0111

Hom.:

193

Bravo

AF:

0.0372

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.102

AC:

449

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.0163

AC:

1975

Asia WGS

AF:

0.0430

AC:

150

AN:

3476

EpiCase

AF:

0.000655

EpiControl

AF:

0.000533

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SLC30A8-related disorder

Benign:1

Sep 24, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.096

.;.;.;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.091

LIST_S2

Benign

0.16

.;T;.;T

MetaRNN

Benign

0.0015

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.070

.;.;.;N

PhyloP100

-0.058

PrimateAI

Benign

0.17

PROVEAN

Benign

-0.12

N;N;N;N

REVEL

Benign

0.030

Sift

Benign

0.099

T;T;T;T

Sift4G

Benign

0.25

T;T;T;T

Polyphen

0.0040

.;.;.;B

Vest4

0.035

MPC

0.051

ClinPred

0.0057

GERP RS

-2.3

Varity_R

0.068

gMVP

0.28

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over