Variant rs2977838 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_130849.4(SLC39A4):c.751C>T(p.Arg251Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0436 in 1,611,662 control chromosomes in the GnomAD database, including 1,877 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/6 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R251Q) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.032 ( 109 hom., cov: 33)

Exomes 𝑓: 0.045 ( 1768 hom. )

Consequence

SLC39A4
NM_130849.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.318

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004521966).

BP6

Variant 8-144415027-G-A is Benign according to our data. Variant chr8-144415027-G-A is described in ClinVar as [Benign]. Clinvar id is 774671.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0519 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC39A4	NM_130849.4 linkuse as main transcript	c.751C>T	p.Arg251Trp	missense_variant	4/12	ENST00000301305.8
LOC124902041	XR_007061145.1 linkuse as main transcript	n.496G>A		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC39A4	ENST00000301305.8 linkuse as main transcript	c.751C>T	p.Arg251Trp	missense_variant	4/12	1	NM_130849.4	P1	Q6P5W5-1
SLC39A4	ENST00000276833.9 linkuse as main transcript	c.676C>T	p.Arg226Trp	missense_variant	3/11	2			Q6P5W5-2
SLC39A4	ENST00000526658.1 linkuse as main transcript	c.469C>T	p.Arg157Trp	missense_variant	3/4	3

Frequencies

GnomAD3 genomes

AF:

0.0319

AC:

4858

AN:

152136

Hom.:

109

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00828

Gnomad AMI

AF:

0.0702

Gnomad AMR

AF:

0.0202

Gnomad ASJ

AF:

0.00692

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0108

Gnomad FIN

AF:

0.0495

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.0512

Gnomad OTH

AF:

0.0277

GnomAD4 exome

AF:

0.0448

AC:

65345

AN:

1459408

Hom.:

1768

Cov.:

AF XY:

0.0441

AC XY:

32026

AN XY:

726036

show subpopulations

Gnomad4 AFR exome

AF:

0.00672

Gnomad4 AMR exome

AF:

0.0152

Gnomad4 ASJ exome

AF:

0.00869

Gnomad4 EAS exome

AF:

0.000227

Gnomad4 SAS exome

AF:

0.0159

Gnomad4 FIN exome

AF:

0.0511

Gnomad4 NFE exome

AF:

0.0523

Gnomad4 OTH exome

AF:

0.0341

GnomAD4 genome

AF:

0.0319

AC:

4857

AN:

152254

Hom.:

109

Cov.:

AF XY:

0.0316

AC XY:

2351

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.00826

Gnomad4 AMR

AF:

0.0201

Gnomad4 ASJ

AF:

0.00692

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0108

Gnomad4 FIN

AF:

0.0495

Gnomad4 NFE

AF:

0.0512

Gnomad4 OTH

AF:

0.0274

Alfa

AF:

0.0440

Hom.:

Bravo

AF:

0.0276

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_noAF

Benign

-0.86

CADD

Benign

DEOGEN2

Benign

0.29

.;T;.

LIST_S2

Benign

0.28

T;T;T

MetaRNN

Benign

0.0045

T;T;T

Sift4G

Uncertain

0.058

T;T;.

Vest4

0.081

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.26

Splicing

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