8-117161787-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_173851.3(SLC30A8):c.622G>A(p.Val208Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,613,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

SLC30A8
NM_173851.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.197

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06192264).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC30A8	NM_173851.3 linkuse as main transcript	c.622G>A	p.Val208Ile	missense_variant	5/8	ENST00000456015.7
LOC105375716	XR_007061067.1 linkuse as main transcript	n.819+10828C>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.622G>A	p.Val208Ile	missense_variant	5/8	1	NM_173851.3	P1	Q8IWU4-1
SLC30A8	ENST00000519688.5 linkuse as main transcript	c.475G>A	p.Val159Ile	missense_variant	6/9	1			Q8IWU4-2
SLC30A8	ENST00000521243.5 linkuse as main transcript	c.475G>A	p.Val159Ile	missense_variant	7/10	1			Q8IWU4-2
SLC30A8	ENST00000427715.2 linkuse as main transcript	c.475G>A	p.Val159Ile	missense_variant	8/11	2			Q8IWU4-2

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000958

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251066

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135670

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000116

AC:

AN:

1461676

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

727134

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000199

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152180

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000958

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000378

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 28, 2024

The c.622G>A (p.V208I) alteration is located in exon 5 (coding exon 5) of the SLC30A8 gene. This alteration results from a G to A substitution at nucleotide position 622, causing the valine (V) at amino acid position 208 to be replaced by an isoleucine (I). 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

0.077

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.62

Cadd

Benign

Dann

Benign

0.93

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.11

M_CAP

Benign

0.012

MetaRNN

Benign

0.062

T;T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.60

N;N;N;N

REVEL

Benign

0.071

Sift

Benign

0.19

T;T;T;T

Sift4G

Benign

0.22

T;T;T;T

Polyphen

0.023

.;.;.;B

Vest4

0.059

MutPred

0.36

.;.;.;Loss of ubiquitination at K206 (P = 0.0896);

MVP

0.48

MPC

0.041

ClinPred

0.091

GERP RS

0.20

Varity_R

0.036

gMVP

0.20

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