Variant 8-117171087-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_173851.3(SLC30A8):c.883G>A(p.Asp295Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000992 in 1,612,230 control chromosomes in the GnomAD database, including 2 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00010 ( 2 hom. )

Consequence

SLC30A8
NM_173851.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.98

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.048826516).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC30A8	NM_173851.3 linkuse as main transcript	c.883G>A	p.Asp295Asn	missense_variant	7/8	ENST00000456015.7
LOC105375716	XR_007061067.1 linkuse as main transcript	n.819+1528C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC30A8	ENST00000456015.7 linkuse as main transcript	c.883G>A	p.Asp295Asn	missense_variant	7/8	1	NM_173851.3	P1	Q8IWU4-1
SLC30A8	ENST00000519688.5 linkuse as main transcript	c.736G>A	p.Asp246Asn	missense_variant	8/9	1			Q8IWU4-2
SLC30A8	ENST00000521243.5 linkuse as main transcript	c.736G>A	p.Asp246Asn	missense_variant	9/10	1			Q8IWU4-2
SLC30A8	ENST00000427715.2 linkuse as main transcript	c.736G>A	p.Asp246Asn	missense_variant	10/11	2			Q8IWU4-2

Frequencies

GnomAD3 genomes

AF:

0.0000592

AC:

AN:

152018

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000830

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000185

AC:

AN:

249298

Hom.:

AF XY:

0.000252

AC XY:

AN XY:

134670

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00132

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000533

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000103

AC:

151

AN:

1460094

Hom.:

Cov.:

AF XY:

0.000142

AC XY:

103

AN XY:

726360

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

Gnomad4 AMR exome

AF:

0.0000225

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00112

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.0000333

Gnomad4 OTH exome

AF:

0.000166

GnomAD4 genome

AF:

0.0000592

AC:

AN:

152136

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000831

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.000206

AC:

EpiCase

AF:

0.0000546

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 15, 2023

The c.883G>A (p.D295N) alteration is located in exon 7 (coding exon 7) of the SLC30A8 gene. This alteration results from a G to A substitution at nucleotide position 883, causing the aspartic acid (D) at amino acid position 295 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.52

Cadd

Benign

Dann

Uncertain

0.99

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.19

FATHMM_MKL

Uncertain

0.82

M_CAP

Benign

0.016

MetaRNN

Benign

0.049

T;T;T;T

MetaSVM

Benign

-0.96

MutationTaster

Benign

0.97

D;D;D;D

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.8

N;N;N;N

REVEL

Benign

0.047

Sift

Benign

0.18

T;T;T;T

Sift4G

Benign

0.12

T;T;T;T

Polyphen

0.23

.;.;.;B

Vest4

0.16

MutPred

0.49

.;.;.;Loss of sheet (P = 0.1158);

MVP

0.53

MPC

0.049

ClinPred

0.083

GERP RS

3.1

Varity_R

0.095

gMVP

0.35

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