Variant 14-20999754-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_014579.4(SLC39A2):c.128T>G(p.Leu43Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.694 in 1,613,402 control chromosomes in the GnomAD database, including 391,529 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.75 ( 43152 hom., cov: 31)

Exomes 𝑓: 0.69 ( 348377 hom. )

Consequence

SLC39A2
NM_014579.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.419

Variant links:

Genes affected

SLC39A2 (HGNC:17127): (solute carrier family 39 member 2) This gene encodes a member of the ZIP family of metal ion transporters. The encoded protein functions as a zinc transporter. Mutations in this gene may be associated with susceptibility to carotid artery disease. Multiple transcript variants have been described. [provided by RefSeq, Mar 2010]

SLC39A2 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.2318908E-6).

BP6

Variant 14-20999754-T-G is Benign according to our data. Variant chr14-20999754-T-G is described in ClinVar as [Benign]. Clinvar id is 1243818.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.885 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC39A2	NM_014579.4 linkuse as main transcript	c.128T>G	p.Leu43Arg	missense_variant	2/4	ENST00000298681.5
SLC39A2	NM_001256588.2 linkuse as main transcript	c.128T>G	p.Leu43Arg	missense_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC39A2	ENST00000298681.5 linkuse as main transcript	c.128T>G	p.Leu43Arg	missense_variant	2/4	1	NM_014579.4	P1	Q9NP94-1
SLC39A2	ENST00000554422.5 linkuse as main transcript	c.128T>G	p.Leu43Arg	missense_variant	2/4	1			Q9NP94-2
	ENST00000647921.1 linkuse as main transcript	n.474A>C		non_coding_transcript_exon_variant	2/5
SLC39A2	ENST00000554128.1 linkuse as main transcript	n.284T>G		non_coding_transcript_exon_variant	2/2	4

Frequencies

GnomAD3 genomes

AF:

0.746

AC:

113431

AN:

151964

Hom.:

43092

Cov.:

show subpopulations

Gnomad AFR

AF:

0.893

Gnomad AMI

AF:

0.730

Gnomad AMR

AF:

0.738

Gnomad ASJ

AF:

0.755

Gnomad EAS

AF:

0.717

Gnomad SAS

AF:

0.638

Gnomad FIN

AF:

0.714

Gnomad MID

AF:

0.709

Gnomad NFE

AF:

0.674

Gnomad OTH

AF:

0.747

GnomAD3 exomes

AF:

0.701

AC:

176168

AN:

251294

Hom.:

62308

AF XY:

0.697

AC XY:

94641

AN XY:

135854

show subpopulations

Gnomad AFR exome

AF:

0.897

Gnomad AMR exome

AF:

0.696

Gnomad ASJ exome

AF:

0.751

Gnomad EAS exome

AF:

0.725

Gnomad SAS exome

AF:

0.643

Gnomad FIN exome

AF:

0.718

Gnomad NFE exome

AF:

0.679

Gnomad OTH exome

AF:

0.694

GnomAD4 exome

AF:

0.689

AC:

1006483

AN:

1461322

Hom.:

348377

Cov.:

AF XY:

0.687

AC XY:

499300

AN XY:

727002

show subpopulations

Gnomad4 AFR exome

AF:

0.905

Gnomad4 AMR exome

AF:

0.703

Gnomad4 ASJ exome

AF:

0.749

Gnomad4 EAS exome

AF:

0.739

Gnomad4 SAS exome

AF:

0.639

Gnomad4 FIN exome

AF:

0.712

Gnomad4 NFE exome

AF:

0.680

Gnomad4 OTH exome

AF:

0.705

GnomAD4 genome

AF:

0.747

AC:

113546

AN:

152080

Hom.:

43152

Cov.:

AF XY:

0.747

AC XY:

55544

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.893

Gnomad4 AMR

AF:

0.737

Gnomad4 ASJ

AF:

0.755

Gnomad4 EAS

AF:

0.718

Gnomad4 SAS

AF:

0.639

Gnomad4 FIN

AF:

0.714

Gnomad4 NFE

AF:

0.674

Gnomad4 OTH

AF:

0.744

Alfa

AF:

0.692

Hom.:

36744

Bravo

AF:

0.765

TwinsUK

AF:

0.688

AC:

2551

ALSPAC

AF:

0.683

AC:

2632

ESP6500AA

AF:

0.913

AC:

4022

ESP6500EA

AF:

0.675

AC:

5807

ExAC

AF:

0.702

AC:

85183

EpiCase

AF:

0.681

EpiControl

AF:

0.689

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 25, 2021	This variant is associated with the following publications: (PMID: 26643924) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.040

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.67

CADD

Benign

3.9

DANN

Benign

0.54

DEOGEN2

Benign

0.025

.;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0016

LIST_S2

Benign

0.26

T;T

MetaRNN

Benign

0.0000012

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-1.2

N;N

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.28

PROVEAN

Benign

3.0

N;N

REVEL

Benign

0.063

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

.;B

Vest4

0.15

MPC

0.043

ClinPred

0.0051

GERP RS

2.8

Varity_R

0.12

gMVP

0.44

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