Variant 14-21000165-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014579.4(SLC39A2):c.296A>T(p.His99Leu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,611,136 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SLC39A2
NM_014579.4 missense, splice_region

Scores

Splicing: ADA: 0.04751

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0550

Variant links:

Genes affected

SLC39A2 (HGNC:17127): (solute carrier family 39 member 2) This gene encodes a member of the ZIP family of metal ion transporters. The encoded protein functions as a zinc transporter. Mutations in this gene may be associated with susceptibility to carotid artery disease. Multiple transcript variants have been described. [provided by RefSeq, Mar 2010]

SLC39A2 links:

ENSG00000258471 (HGNC:):

ENSG00000258471 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07771233).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC39A2	NM_014579.4 linkuse as main transcript	c.296A>T	p.His99Leu	missense_variant, splice_region_variant	3/4	ENST00000298681.5	NP_055394.2	Q9NP94-1
SLC39A2	NM_001256588.2 linkuse as main transcript	c.*33A>T		splice_region_variant	3/4		NP_001243517.1	Q9NP94-2
SLC39A2	NM_001256588.2 linkuse as main transcript	c.*33A>T		3_prime_UTR_variant	3/4		NP_001243517.1	Q9NP94-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SLC39A2	ENST00000298681.5 linkuse as main transcript	c.296A>T	p.His99Leu	missense_variant, splice_region_variant	3/4	1	NM_014579.4	ENSP00000298681.4	Q9NP94-1
SLC39A2	ENST00000554422.5 linkuse as main transcript	c.*33A>T		splice_region_variant	3/4	1		ENSP00000452568.1	Q9NP94-2
SLC39A2	ENST00000554422.5 linkuse as main transcript	c.*33A>T		3_prime_UTR_variant	3/4	1		ENSP00000452568.1	Q9NP94-2
ENSG00000258471	ENST00000647921.1 linkuse as main transcript	n.398-335T>A		intron_variant

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1458972

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725962

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

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

AF:

0.00000657

AC:

AN:

152164

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 13, 2024

The c.296A>T (p.H99L) alteration is located in exon 3 (coding exon 3) of the SLC39A2 gene. This alteration results from a A to T substitution at nucleotide position 296, causing the histidine (H) at amino acid position 99 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.65

CADD

Benign

0.97

DANN

Benign

0.79

DEOGEN2

Benign

0.039

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.030

LIST_S2

Benign

0.26

M_CAP

Benign

0.0026

MetaRNN

Benign

0.078

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.1

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.1

REVEL

Benign

0.053

Sift

Benign

0.37

Sift4G

Benign

0.20

Polyphen

0.0020

Vest4

0.082

MutPred

0.62

Loss of disorder (P = 0.0448);

MVP

0.20

MPC

0.039

ClinPred

0.17

GERP RS

-3.8

Varity_R

0.097

gMVP

0.32

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.048

dbscSNV1_RF

Benign

0.49

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