Variant 8-144412594-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PS1_ModeratePM2PP3_ModeratePP5_Moderate

The NM_130849.4(SLC39A4):c.1888G>C(p.Gly630Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,872 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely pathogenicin UniProt.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SLC39A4
NM_130849.4 missense

Scores

Clinical Significance

Likely pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: -1.28

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 8 ACMG points.

PS1

Transcript NM_130849.4 (SLC39A4) is affected with MISSENSE_VARIANT having same AA change as one Pathogenic present in UniProt

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.908

PP5

Variant 8-144412594-C-G is Pathogenic according to our data. Variant chr8-144412594-C-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 2433455.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC39A4	NM_130849.4 linkuse as main transcript	c.1888G>C	p.Gly630Arg	missense_variant	12/12	ENST00000301305.8	NP_570901.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC39A4	ENST00000301305.8 linkuse as main transcript	c.1888G>C	p.Gly630Arg	missense_variant	12/12	1	NM_130849.4	ENSP00000301305	P1	Q6P5W5-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461872

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Hereditary acrodermatitis enteropathica

Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

Revvity Omics, Revvity

Jan 30, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.89

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

-0.080

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

.;T

Eigen

Benign

0.038

Eigen_PC

Benign

-0.088

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.76

T;T

M_CAP

Pathogenic

0.37

MetaRNN

Pathogenic

0.91

D;D

MetaSVM

Benign

-0.60

MutationAssessor

Uncertain

2.4

.;M

MutationTaster

Benign

0.52

N;N

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-0.72

N;N

REVEL

Benign

0.29

Sift

Benign

0.050

D;T

Sift4G

Benign

0.37

T;T

Polyphen

0.95

.;P

Vest4

0.53

MutPred

0.96

.;Gain of methylation at G630 (P = 0.0108);

MVP

0.71

MPC

0.49

ClinPred

0.72

GERP RS

1.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.73

gMVP

0.55

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over