8-117172545-G-A

Position:

chr8-117172545-G-A

Variant summary

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

The ENST00000456015.7(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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. 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
ENST00000456015.7 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.0580

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=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 id 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/exons	MANE	Protein	UniProt
SLC30A8	NM_173851.3 linkuse as main transcript	c.974G>A	p.Arg325Gln	missense_variant	8/8	ENST00000456015.7	NP_776250.2
LOC105375716	XR_007061067.1 linkuse as main transcript	n.819+70C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC30A8	ENST00000456015.7 linkuse as main transcript	c.974G>A	p.Arg325Gln	missense_variant	8/8	1	NM_173851.3	ENSP00000415011	P1	Q8IWU4-1
SLC30A8	ENST00000519688.5 linkuse as main transcript	c.827G>A	p.Arg276Gln	missense_variant	9/9	1		ENSP00000431069		Q8IWU4-2
SLC30A8	ENST00000521243.5 linkuse as main transcript	c.827G>A	p.Arg276Gln	missense_variant	10/10	1		ENSP00000428545		Q8IWU4-2
SLC30A8	ENST00000427715.2 linkuse as main transcript	c.827G>A	p.Arg276Gln	missense_variant	11/11	2		ENSP00000407505		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

GnomAD3 exomes

AF:

0.0145

AC:

3620

AN:

249532

Hom.:

163

AF XY:

0.0122

AC XY:

1653

AN XY:

134998

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 SAS exome

AF:

0.00294

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

Gnomad4 AFR exome

AF:

0.107

Gnomad4 AMR exome

AF:

0.00667

Gnomad4 ASJ exome

AF:

0.00172

Gnomad4 EAS exome

AF:

0.0604

Gnomad4 SAS exome

AF:

0.00306

Gnomad4 FIN exome

AF:

0.000225

Gnomad4 NFE exome

AF:

0.000368

Gnomad4 OTH exome

AF:

0.0119

GnomAD4 genome

AF:

0.0331

AC:

5041

AN:

152234

Hom.:

248

Cov.:

AF XY:

0.0327

AC XY:

2431

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.105

Gnomad4 AMR

AF:

0.0124

Gnomad4 ASJ

AF:

0.00259

Gnomad4 EAS

AF:

0.0721

Gnomad4 SAS

AF:

0.00394

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.000632

Gnomad4 OTH

AF:

0.0246

Alfa

AF:

0.00525

Hom.:

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

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 24, 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). -

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

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

MutationTaster

Benign

1.0

N;N;N;N

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

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