5-69115315-G-A

Position:

chr5-69115315-G-A

Variant summary

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

The ENST00000396591.8(SLC30A5):c.691G>A(p.Val231Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000929 in 1,614,002 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V231A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000093 ( 0 hom. )

Consequence

SLC30A5
ENST00000396591.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.08

Variant links:

Genes affected

SLC30A5 (HGNC:19089): (solute carrier family 30 member 5) This gene encodes a member of the SLC30A/ZnT family of zinc transporter proteins. ZnT proteins mediate both cellular zinc efflux and zinc sequestration into membrane-bound organelles. The encoded protein plays a role in the early secretory pathway as a heterodimer with zinc transporter 6, and may also regulate zinc sequestration into secretory granules of pancreatic beta cells. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and a pseudogene of this gene is located on the long arm of chromosome 19. [provided by RefSeq, Oct 2011]

SLC30A5 links:

(HGNC:):

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=0.03634715).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SLC30A5	NM_022902.5 linkuse as main transcript	c.691G>A	p.Val231Ile	missense_variant	8/16	ENST00000396591.8	NP_075053.2
SLC30A5	XM_005248569.4 linkuse as main transcript	c.568G>A	p.Val190Ile	missense_variant	7/15		XP_005248626.1
SLC30A5	XM_006714672.5 linkuse as main transcript	c.691G>A	p.Val231Ile	missense_variant	8/15		XP_006714735.1
SLC30A5	XM_017009749.2 linkuse as main transcript	c.568G>A	p.Val190Ile	missense_variant	7/14		XP_016865238.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC30A5	ENST00000396591.8 linkuse as main transcript	c.691G>A	p.Val231Ile	missense_variant	8/16	1	NM_022902.5	ENSP00000379836	P1	Q8TAD4-1
SLC30A5	ENST00000507354.5 linkuse as main transcript	n.889G>A		non_coding_transcript_exon_variant	5/11	1
	ENST00000690195.2 linkuse as main transcript	n.770C>T		non_coding_transcript_exon_variant	5/6
	ENST00000504129.1 linkuse as main transcript	n.696C>T		non_coding_transcript_exon_variant	5/6	5

Frequencies

GnomAD3 genomes

AF:

0.0000921

AC:

AN:

152060

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000915

AC:

AN:

251474

Hom.:

AF XY:

0.0000736

AC XY:

AN XY:

135916

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000185

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000930

AC:

136

AN:

1461824

Hom.:

Cov.:

AF XY:

0.0000935

AC XY:

AN XY:

727208

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000112

Gnomad4 OTH exome

AF:

0.000132

GnomAD4 genome

AF:

0.0000920

AC:

AN:

152178

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.000144

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000112

Hom.:

Bravo

AF:

0.0000680

ExAC

AF:

0.0000988

AC:

EpiCase

AF:

0.000164

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

Oct 20, 2021

The c.691G>A (p.V231I) alteration is located in exon 8 (coding exon 8) of the SLC30A5 gene. This alteration results from a G to A substitution at nucleotide position 691, causing the valine (V) at amino acid position 231 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

0.071

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.55

CADD

Benign

6.5

DANN

Benign

0.61

DEOGEN2

Benign

0.075

Eigen

Benign

-0.99

Eigen_PC

Benign

-0.84

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.84

M_CAP

Benign

0.022

MetaRNN

Benign

0.036

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.51

MutationTaster

Benign

1.0

PrimateAI

Benign

0.27

PROVEAN

Benign

0.0

REVEL

Benign

0.045

Sift

Benign

0.86

Sift4G

Benign

1.0

Polyphen

0.13

Vest4

0.097

MutPred

0.22

Loss of sheet (P = 0.0817);

MVP

0.28

MPC

0.34

ClinPred

0.0069

GERP RS

-0.0082

Varity_R

0.017

gMVP

0.068

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