Genetic Variant SLC39A2:p.Phe32Leu (chr14-20999540-T-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_014579.4(SLC39A2):c.94T>C(p.Phe32Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000805 in 1,613,988 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

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

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

SLC39A2
NM_014579.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.36

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.42081696).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC39A2	NM_014579.4 link	c.94T>C	p.Phe32Leu	missense_variant	Exon 1 of 4	ENST00000298681.5	NP_055394.2	Q9NP94-1
SLC39A2	NM_001256588.2 link	c.94T>C	p.Phe32Leu	missense_variant	Exon 1 of 4		NP_001243517.1	Q9NP94-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC39A2	ENST00000298681.5 link	c.94T>C	p.Phe32Leu	missense_variant	Exon 1 of 4	1	NM_014579.4	ENSP00000298681.4	Q9NP94-1
SLC39A2	ENST00000554422.5 link	c.94T>C	p.Phe32Leu	missense_variant	Exon 1 of 4	1		ENSP00000452568.1	Q9NP94-2
SLC39A2	ENST00000554128.1 link	n.250T>C		non_coding_transcript_exon_variant	Exon 1 of 2	4
ENSG00000258471	ENST00000647921.1 link	n.538+150A>G		intron_variant	Intron 2 of 4

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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

GnomAD3 exomes

AF:

0.0000398

AC:

AN:

251454

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000231

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000821

AC:

AN:

1461692

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727150

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

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:

152296

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000653

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:

0.0000189

ExAC

AF:

0.0000494

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 28, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.94T>C (p.F32L) alteration is located in exon 1 (coding exon 1) of the SLC39A2 gene. This alteration results from a T to C substitution at nucleotide position 94, causing the phenylalanine (F) at amino acid position 32 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

Pathogenic

0.86

BayesDel_addAF

Benign

-0.071

BayesDel_noAF

Uncertain

-0.040

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.045

.;T

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.73

T;T

M_CAP

Benign

0.027

MetaRNN

Benign

0.42

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.7

L;L

PrimateAI

Uncertain

0.56

PROVEAN

Pathogenic

-4.8

D;N

REVEL

Uncertain

0.36

Sift

Pathogenic

0.0

D;T

Sift4G

Pathogenic

0.0

D;T

Polyphen

1.0

.;D

Vest4

0.73

MutPred

0.60

Gain of helix (P = 0.0325);Gain of helix (P = 0.0325);

MVP

0.25

MPC

0.27

ClinPred

0.76

GERP RS

5.2

Varity_R

0.57

gMVP

0.39

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