8-144415944-C-T

Position:

chr8-144415944-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.340G>A(p.Ala114Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.491 in 1,591,926 control chromosomes in the GnomAD database, including 195,443 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 0.44 ( 15453 hom., cov: 33)

Exomes 𝑓: 0.50 ( 179990 hom. )

Consequence

SLC39A4
NM_130849.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.383

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=1.969787E-5).

BP6

Variant 8-144415944-C-T is Benign according to our data. Variant chr8-144415944-C-T is described in ClinVar as [Benign]. Clinvar id is 362260.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144415944-C-T is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.515 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.340G>A	p.Ala114Thr	missense_variant	2/12	ENST00000301305.8	NP_570901.3	Q6P5W5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SLC39A4	ENST00000301305.8 linkuse as main transcript	c.340G>A	p.Ala114Thr	missense_variant	2/12	1	NM_130849.4	ENSP00000301305.4	Q6P5W5-1
SLC39A4	ENST00000276833.9 linkuse as main transcript	c.265G>A	p.Ala89Thr	missense_variant	1/11	2		ENSP00000276833.5	Q6P5W5-2
SLC39A4	ENST00000526658.1 linkuse as main transcript	c.193-525G>A		intron_variant		3		ENSP00000434512.1	E9PQ16

Frequencies

GnomAD3 genomes

AF:

0.439

AC:

66765

AN:

151934

Hom.:

15455

Cov.:

show subpopulations

Gnomad AFR

AF:

0.297

Gnomad AMI

AF:

0.456

Gnomad AMR

AF:

0.410

Gnomad ASJ

AF:

0.598

Gnomad EAS

AF:

0.383

Gnomad SAS

AF:

0.381

Gnomad FIN

AF:

0.518

Gnomad MID

AF:

0.585

Gnomad NFE

AF:

0.520

Gnomad OTH

AF:

0.446

GnomAD3 exomes

AF:

0.458

AC:

97205

AN:

212328

Hom.:

22840

AF XY:

0.464

AC XY:

53849

AN XY:

116026

show subpopulations

Gnomad AFR exome

AF:

0.286

Gnomad AMR exome

AF:

0.374

Gnomad ASJ exome

AF:

0.595

Gnomad EAS exome

AF:

0.368

Gnomad SAS exome

AF:

0.391

Gnomad FIN exome

AF:

0.517

Gnomad NFE exome

AF:

0.519

Gnomad OTH exome

AF:

0.485

GnomAD4 exome

AF:

0.496

AC:

714316

AN:

1439874

Hom.:

179990

Cov.:

AF XY:

0.494

AC XY:

353224

AN XY:

714592

show subpopulations

Gnomad4 AFR exome

AF:

0.297

Gnomad4 AMR exome

AF:

0.376

Gnomad4 ASJ exome

AF:

0.592

Gnomad4 EAS exome

AF:

0.386

Gnomad4 SAS exome

AF:

0.393

Gnomad4 FIN exome

AF:

0.512

Gnomad4 NFE exome

AF:

0.515

Gnomad4 OTH exome

AF:

0.497

GnomAD4 genome

AF:

0.439

AC:

66786

AN:

152052

Hom.:

15453

Cov.:

AF XY:

0.438

AC XY:

32592

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.297

Gnomad4 AMR

AF:

0.410

Gnomad4 ASJ

AF:

0.598

Gnomad4 EAS

AF:

0.382

Gnomad4 SAS

AF:

0.381

Gnomad4 FIN

AF:

0.518

Gnomad4 NFE

AF:

0.520

Gnomad4 OTH

AF:

0.447

Alfa

AF:

0.504

Hom.:

6230

Bravo

AF:

0.425

TwinsUK

AF:

0.512

AC:

1898

ALSPAC

AF:

0.503

AC:

1940

ESP6500AA

AF:

0.284

AC:

1238

ESP6500EA

AF:

0.512

AC:

4378

ExAC

AF:

0.433

AC:

51499

Asia WGS

AF:

0.385

AC:

1341

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

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 09, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
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

0.094

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.67

CADD

Benign

8.3

DANN

Benign

0.93

DEOGEN2

Benign

0.018

.;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.032

LIST_S2

Benign

0.74

T;T

MetaRNN

Benign

0.000020

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.69

.;N

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.17

N;N

REVEL

Benign

0.059

Sift

Benign

1.0

T;T

Sift4G

Benign

0.20

T;T

Polyphen

0.43

.;B

Vest4

0.047

MPC

0.20

ClinPred

0.0093

GERP RS

-3.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.019

gMVP

0.35

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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