Variant chr1-26045188-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001004434.3(SLC30A2):c.80G>A(p.Gly27Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000319 in 1,612,338 control chromosomes in the GnomAD database, including 3 homozygotes. 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 0.0016 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00019 ( 2 hom. )

Consequence

SLC30A2
NM_001004434.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.271

Variant links:

Genes affected

SLC30A2 (HGNC:11013): (solute carrier family 30 member 2) The protein encoded by this gene is a zinc transporter that acts as a homodimer. The encoded protein plays a role in secreting zinc into breast milk. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2015]

SLC30A2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004112661).

BS2

High AC in GnomAd4 at 243 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC30A2	NM_001004434.3 linkuse as main transcript	c.80G>A	p.Gly27Glu	missense_variant	2/8	ENST00000374276.4
SLC30A2	NM_032513.5 linkuse as main transcript	c.80G>A	p.Gly27Glu	missense_variant	2/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC30A2	ENST00000374276.4 linkuse as main transcript	c.80G>A	p.Gly27Glu	missense_variant	2/8	1	NM_001004434.3	P1	Q9BRI3-2
SLC30A2	ENST00000374278.7 linkuse as main transcript	c.80G>A	p.Gly27Glu	missense_variant	2/7	1			Q9BRI3-1
SLC30A2	ENST00000498060.1 linkuse as main transcript	n.264G>A		non_coding_transcript_exon_variant	1/3	5

Frequencies

GnomAD3 genomes

AF:

0.00160

AC:

243

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00565

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000380

AC:

AN:

250064

Hom.:

AF XY:

0.000288

AC XY:

AN XY:

135434

show subpopulations

Gnomad AFR exome

AF:

0.00550

Gnomad AMR exome

AF:

0.000145

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:

0.00000886

Gnomad OTH exome

AF:

0.000328

GnomAD4 exome

AF:

0.000186

AC:

271

AN:

1459986

Hom.:

Cov.:

AF XY:

0.000164

AC XY:

119

AN XY:

726298

show subpopulations

Gnomad4 AFR exome

AF:

0.00736

Gnomad4 AMR exome

AF:

0.000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.000199

GnomAD4 genome

AF:

0.00159

AC:

243

AN:

152352

Hom.:

Cov.:

AF XY:

0.00141

AC XY:

105

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.00563

Gnomad4 AMR

AF:

0.000457

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000359

Hom.:

Bravo

AF:

0.00180

ESP6500AA

AF:

0.00568

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000461

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 13, 2024

The c.80G>A (p.G27E) alteration is located in exon 2 (coding exon 2) of the SLC30A2 gene. This alteration results from a G to A substitution at nucleotide position 80, causing the glycine (G) at amino acid position 27 to be replaced by a glutamic acid (E). 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

0.079

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.54

CADD

Benign

9.2

DANN

Benign

0.28

DEOGEN2

Benign

0.13

T;.

Eigen

Benign

-0.89

Eigen_PC

Benign

-0.87

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.68

T;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.0041

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

L;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.34

PROVEAN

Benign

-1.2

N;N

REVEL

Benign

0.046

Sift

Benign

0.76

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;B

Vest4

0.25

MVP

0.10

MPC

0.37

ClinPred

0.0017

GERP RS

2.6

Varity_R

0.047

gMVP

0.51

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