Variant 8-117172545-G-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_173851.3(SLC30A8):c.974G>T(p.Arg325Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,318 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. 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: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SLC30A8
NM_173851.3 missense

Scores

Clinical Significance

Not reported in ClinVar

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:

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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=0.06322262).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC30A8	NM_173851.3 linkuse as main transcript	c.974G>T	p.Arg325Leu	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.974G>T	p.Arg325Leu	missense_variant	8/8	1	NM_173851.3	ENSP00000415011.2	Q8IWU4-1
SLC30A8	ENST00000519688.5 linkuse as main transcript	c.827G>T	p.Arg276Leu	missense_variant	9/9	1		ENSP00000431069.1	Q8IWU4-2
SLC30A8	ENST00000521243.5 linkuse as main transcript	c.827G>T	p.Arg276Leu	missense_variant	10/10	1		ENSP00000428545.1	Q8IWU4-2
SLC30A8	ENST00000427715.2 linkuse as main transcript	c.827G>T	p.Arg276Leu	missense_variant	11/11	2		ENSP00000407505.2	Q8IWU4-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249532

Hom.:

AF XY:

0.00000741

AC XY:

AN XY:

134998

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:

0.00000137

AC:

AN:

1461318

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726974

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.00000370

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.47

CADD

Benign

7.2

DANN

Benign

0.97

DEOGEN2

Benign

0.098

.;.;.;T

Eigen

Benign

-0.97

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.053

LIST_S2

Benign

0.31

.;T;.;T

M_CAP

Benign

0.030

MetaRNN

Benign

0.063

T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.55

.;.;.;N

PrimateAI

Benign

0.17

PROVEAN

Benign

-0.31

N;N;N;N

REVEL

Benign

0.033

Sift

Benign

0.039

D;D;D;D

Sift4G

Benign

0.13

T;T;T;T

Polyphen

0.011

.;.;.;B

Vest4

0.17

MutPred

0.40

.;.;.;Loss of MoRF binding (P = 0.0143);

MVP

0.27

MPC

0.061

ClinPred

0.054

GERP RS

-2.3

Varity_R

0.14

gMVP

0.43

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over