8-144414851-C-T

Position:

• chr8-144414851-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_130849.4(SLC39A4):​c.850G>A​(p.Glu284Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00513 in 1,613,336 control chromosomes in the GnomAD database, including 320 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.027 (163 hom., cov: 33)
  • Exomes 𝑓: 0.0028 (157 hom.)
• Consequence: SLC39A4 NM_130849.4 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 1.46

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]

LOC124902041 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0023306906).
• BP6: Variant 8-144414851-C-T is Benign according to our data. Variant chr8-144414851-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 362247.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0926 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC39A4	NM_130849.4	c.850G>A	p.Glu284Lys	missense_variant	5/12	ENST00000301305.8	NP_570901.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC39A4	ENST00000301305.8	c.850G>A	p.Glu284Lys	missense_variant	5/12	1	NM_130849.4	ENSP00000301305.4
SLC39A4	ENST00000276833.9	c.775G>A	p.Glu259Lys	missense_variant	4/11	2		ENSP00000276833.5
SLC39A4	ENST00000526658.1	c.*15G>A		downstream_gene_variant		3		ENSP00000434512.1

Frequencies

GnomAD3 genomes AF: 0.0274 AC: 4162 AN: 152102 Hom.: 163 Cov.: 33

Gnomad AFR AF: 0.0952

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0103

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.0196

GnomAD3 exomes AF: 0.00737 AC: 1850 AN: 251038 Hom.: 74 AF XY: 0.00559 AC XY: 759 AN XY: 135830

Gnomad AFR exome AF: 0.0999

Gnomad AMR exome AF: 0.00480

Gnomad ASJ exome AF: 0.0000994

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000344

Gnomad OTH exome AF: 0.00294

GnomAD4 exome AF: 0.00282 AC: 4118 AN: 1461116 Hom.: 157 Cov.: 33 AF XY: 0.00240 AC XY: 1747 AN XY: 726904

Gnomad4 AFR exome AF: 0.0944

Gnomad4 AMR exome AF: 0.00539

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000174

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000286

Gnomad4 OTH exome AF: 0.00608

GnomAD4 genome AF: 0.0274 AC: 4166 AN: 152220 Hom.: 163 Cov.: 33 AF XY: 0.0265 AC XY: 1976 AN XY: 74446

Gnomad4 AFR AF: 0.0951

Gnomad4 AMR AF: 0.0103

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000250

Gnomad4 OTH AF: 0.0194

Alfa AF: 0.00534 Hom.: 57

Bravo AF: 0.0310

ESP6500AA AF: 0.0890 AC: 392

ESP6500EA AF: 0.000349 AC: 3

ExAC AF: 0.00893 AC: 1084

Asia WGS AF: 0.00375 AC: 13 AN: 3478

EpiCase AF: 0.000491

EpiControl AF: 0.000178

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Jan 24, 2017	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Hereditary acrodermatitis enteropathica Benign:2

Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -
Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Apr 28, 2017	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	.;T
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.22
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.85	D;D
MetaRNN	Benign	0.0023	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	.;L
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-1.6	N;N
REVEL	Uncertain	0.34
Sift	Benign	0.42	T;T
Sift4G	Benign	0.12	T;T
Polyphen		0.90	.;P
Vest4		0.49
MVP		0.54
MPC		0.49
ClinPred		0.021	T
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.083
gMVP		0.39

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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

Other links and lift over

dbSNP: rs7823979; hg19: chr8-145640235;