rs2280838

Positions:

chr8-144416618-C-T

Variant summary

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

The NM_130849.4(SLC39A4):c.172G>A(p.Ala58Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 1,594,344 control chromosomes in the GnomAD database, including 239,184 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 0.51 ( 20470 hom., cov: 33)

Exomes 𝑓: 0.55 ( 218714 hom. )

Consequence

SLC39A4
NM_130849.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -3.20

Variant links:

Genes affected

SLC39A4 (HGNC:17129): (solute carrier family 39 member 4) This gene encodes a member of the zinc/iron-regulated transporter-like protein (ZIP) family. The encoded protein localizes to cell membranes and is required for zinc uptake in the intestine. Mutations in this gene result in acrodermatitis enteropathica. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2013]

SLC39A4 links:

LOC124902041 (HGNC:):

LOC124902041 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=6.3947305E-6).

BP6

Variant 8-144416618-C-T is Benign according to our data. Variant chr8-144416618-C-T is described in ClinVar as [Benign]. Clinvar id is 362265.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144416618-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.565 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC39A4	NM_130849.4 linkuse as main transcript	c.172G>A	p.Ala58Thr	missense_variant	1/12	ENST00000301305.8	NP_570901.3	Q6P5W5-1
SLC39A4	NM_001374839.1 linkuse as main transcript	c.172G>A	p.Ala58Thr	missense_variant	1/11		NP_001361768.1
SLC39A4	XM_024447189.2 linkuse as main transcript	c.172G>A	p.Ala58Thr	missense_variant	1/10		XP_024302957.1
LOC124902041	XR_007061145.1 linkuse as main transcript	n.2087C>T		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC39A4	ENST00000301305.8 linkuse as main transcript	c.172G>A	p.Ala58Thr	missense_variant	1/12	1	NM_130849.4	ENSP00000301305.4		Q6P5W5-1
SLC39A4	ENST00000526658.1 linkuse as main transcript	c.172G>A	p.Ala58Thr	missense_variant	1/4	3		ENSP00000434512.1		E9PQ16

Frequencies

GnomAD3 genomes

AF:

0.514

AC:

78006

AN:

151892

Hom.:

20468

Cov.:

show subpopulations

Gnomad AFR

AF:

0.442

Gnomad AMI

AF:

0.493

Gnomad AMR

AF:

0.458

Gnomad ASJ

AF:

0.636

Gnomad EAS

AF:

0.385

Gnomad SAS

AF:

0.448

Gnomad FIN

AF:

0.561

Gnomad MID

AF:

0.646

Gnomad NFE

AF:

0.570

Gnomad OTH

AF:

0.507

GnomAD3 exomes

AF:

0.506

AC:

108910

AN:

215186

Hom.:

28205

AF XY:

0.513

AC XY:

60050

AN XY:

117120

show subpopulations

Gnomad AFR exome

AF:

0.425

Gnomad AMR exome

AF:

0.400

Gnomad ASJ exome

AF:

0.634

Gnomad EAS exome

AF:

0.363

Gnomad SAS exome

AF:

0.464

Gnomad FIN exome

AF:

0.556

Gnomad NFE exome

AF:

0.566

Gnomad OTH exome

AF:

0.527

GnomAD4 exome

AF:

0.547

AC:

789600

AN:

1442334

Hom.:

218714

Cov.:

AF XY:

0.547

AC XY:

391398

AN XY:

716030

show subpopulations

Gnomad4 AFR exome

AF:

0.438

Gnomad4 AMR exome

AF:

0.407

Gnomad4 ASJ exome

AF:

0.632

Gnomad4 EAS exome

AF:

0.388

Gnomad4 SAS exome

AF:

0.468

Gnomad4 FIN exome

AF:

0.554

Gnomad4 NFE exome

AF:

0.565

Gnomad4 OTH exome

AF:

0.544

GnomAD4 genome

AF:

0.513

AC:

78037

AN:

152010

Hom.:

20470

Cov.:

AF XY:

0.511

AC XY:

38007

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.442

Gnomad4 AMR

AF:

0.458

Gnomad4 ASJ

AF:

0.636

Gnomad4 EAS

AF:

0.385

Gnomad4 SAS

AF:

0.447

Gnomad4 FIN

AF:

0.561

Gnomad4 NFE

AF:

0.570

Gnomad4 OTH

AF:

0.507

Alfa

AF:

0.552

Hom.:

19740

Bravo

AF:

0.501

TwinsUK

AF:

0.563

AC:

2086

ALSPAC

AF:

0.548

AC:

2111

ESP6500AA

AF:

0.431

AC:

1886

ESP6500EA

AF:

0.570

AC:

4892

ExAC

AF:

0.484

AC:

57893

Asia WGS

AF:

0.414

AC:

1443

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hereditary acrodermatitis enteropathica

Benign:3

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 10, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 09, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.45

CADD

Benign

0.024

DANN

Benign

0.95

DEOGEN2

Benign

0.019

T;.

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.51

T;T

MetaRNN

Benign

0.0000064

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

L;.

PrimateAI

Benign

0.47

PROVEAN

Benign

0.24

N;N

REVEL

Benign

0.077

Sift

Benign

0.98

T;T

Sift4G

Benign

0.54

T;.

Polyphen

0.0

B;.

Vest4

0.033

MPC

0.12

ClinPred

0.016

GERP RS

-9.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.022

gMVP

0.47

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