rs117535951

Positions:

chr8-144416033-G-A

Variant summary

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

The ENST00000301305.8(SLC39A4):c.251C>T(p.Pro84Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0336 in 1,579,106 control chromosomes in the GnomAD database, including 1,055 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.027 ( 81 hom., cov: 34)

Exomes 𝑓: 0.034 ( 974 hom. )

Consequence

SLC39A4
ENST00000301305.8 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.756

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=0.0023266077).

BP6

Variant 8-144416033-G-A is Benign according to our data. Variant chr8-144416033-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 362263.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-144416033-G-A is described in Lovd as [Likely_benign].

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0543 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.251C>T	p.Pro84Leu	missense_variant	2/12	ENST00000301305.8	NP_570901.3
LOC124902041	XR_007061145.1 linkuse as main transcript	n.1502G>A		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.251C>T	p.Pro84Leu	missense_variant	2/12	1	NM_130849.4	ENSP00000301305	P1	Q6P5W5-1
SLC39A4	ENST00000276833.9 linkuse as main transcript	c.176C>T	p.Pro59Leu	missense_variant	1/11	2		ENSP00000276833		Q6P5W5-2
SLC39A4	ENST00000526658.1 linkuse as main transcript	c.192+565C>T		intron_variant		3		ENSP00000434512

Frequencies

GnomAD3 genomes

AF:

0.0273

AC:

4148

AN:

152098

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00686

Gnomad AMI

AF:

0.0132

Gnomad AMR

AF:

0.0209

Gnomad ASJ

AF:

0.0605

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00827

Gnomad FIN

AF:

0.0643

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.0369

Gnomad OTH

AF:

0.0306

GnomAD3 exomes

AF:

0.0289

AC:

5805

AN:

200566

Hom.:

129

AF XY:

0.0297

AC XY:

3263

AN XY:

109778

show subpopulations

Gnomad AFR exome

AF:

0.00483

Gnomad AMR exome

AF:

0.0172

Gnomad ASJ exome

AF:

0.0571

Gnomad EAS exome

AF:

0.0000639

Gnomad SAS exome

AF:

0.00987

Gnomad FIN exome

AF:

0.0678

Gnomad NFE exome

AF:

0.0383

Gnomad OTH exome

AF:

0.0336

GnomAD4 exome

AF:

0.0343

AC:

48890

AN:

1426892

Hom.:

974

Cov.:

AF XY:

0.0338

AC XY:

23893

AN XY:

705994

show subpopulations

Gnomad4 AFR exome

AF:

0.00617

Gnomad4 AMR exome

AF:

0.0183

Gnomad4 ASJ exome

AF:

0.0577

Gnomad4 EAS exome

AF:

0.0000518

Gnomad4 SAS exome

AF:

0.00951

Gnomad4 FIN exome

AF:

0.0634

Gnomad4 NFE exome

AF:

0.0367

Gnomad4 OTH exome

AF:

0.0380

GnomAD4 genome

AF:

0.0273

AC:

4148

AN:

152214

Hom.:

Cov.:

AF XY:

0.0280

AC XY:

2087

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.00684

Gnomad4 AMR

AF:

0.0209

Gnomad4 ASJ

AF:

0.0605

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.00828

Gnomad4 FIN

AF:

0.0643

Gnomad4 NFE

AF:

0.0369

Gnomad4 OTH

AF:

0.0303

Alfa

AF:

0.0359

Hom.:

Bravo

AF:

0.0236

TwinsUK

AF:

0.0235

AC:

ALSPAC

AF:

0.0394

AC:

152

ESP6500AA

AF:

0.00597

AC:

ESP6500EA

AF:

0.0353

AC:

301

ExAC

AF:

0.0254

AC:

3026

Asia WGS

AF:

0.00779

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hereditary acrodermatitis enteropathica

Benign:4

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 10, 2021	- -
Benign, criteria provided, single submitter	curation	SIB Swiss Institute of Bioinformatics	May 31, 2018	This variant is interpreted as a Benign - Stand Alone, for Acrodermatitis enteropathica, zinc-deficiency type, in Autosomal Recessive manner. The following ACMG Tag(s) were applied: BA1 =>Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. BS1 => Allele frequency is greater than expected for disorder. BS2 => Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age. -
Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Oct 25, 2019	- -

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 06, 2020	This variant is associated with the following publications: (PMID: 28188634, 27884173, 12032886, 20981092, 22995991) -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Likely 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 in 1000Genomes: 44/2178=2% -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.68

CADD

Benign

4.8

DANN

Benign

0.96

DEOGEN2

Benign

0.038

.;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.088

LIST_S2

Benign

0.61

T;T

MetaRNN

Benign

0.0023

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

.;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.4

N;N

REVEL

Benign

0.025

Sift

Uncertain

0.019

D;T

Sift4G

Uncertain

0.019

D;D

Polyphen

0.65

.;P

Vest4

0.068

MPC

0.13

ClinPred

0.0015

GERP RS

-1.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

Varity_R

0.032

gMVP

0.35

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