10-17961740-A-G

Position:

chr10-17961740-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001145195.2(SLC39A12):c.421A>G(p.Lys141Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000483 in 1,613,988 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000044 ( 0 hom. )

Consequence

SLC39A12
NM_001145195.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.428

Variant links:

Genes affected

SLC39A12 (HGNC:20860): (solute carrier family 39 member 12) Zinc is an essential cofactor for hundreds of enzymes. It is involved in protein, nucleic acid, carbohydrate, and lipid metabolism, as well as in the control of gene transcription, growth, development, and differentiation. SLC39A12 belongs to a subfamily of proteins that show structural characteristics of zinc transporters (Taylor and Nicholson, 2003 [PubMed 12659941]).[supplied by OMIM, Aug 2008]

SLC39A12 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0222179).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC39A12	NM_001145195.2 linkuse as main transcript	c.421A>G	p.Lys141Glu	missense_variant	3/13	ENST00000377369.7	NP_001138667.1	Q504Y0-1
SLC39A12	NM_001282733.2 linkuse as main transcript	c.421A>G	p.Lys141Glu	missense_variant	3/13		NP_001269662.1	Q504Y0-4
SLC39A12	NM_152725.4 linkuse as main transcript	c.421A>G	p.Lys141Glu	missense_variant	3/12		NP_689938.2	Q504Y0-3
SLC39A12	NM_001282734.2 linkuse as main transcript	c.19A>G	p.Lys7Glu	missense_variant	2/12		NP_001269663.1	Q504Y0-5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SLC39A12	ENST00000377369.7 linkuse as main transcript	c.421A>G	p.Lys141Glu	missense_variant	3/13	1	NM_001145195.2	ENSP00000366586.2	Q504Y0-1
SLC39A12	ENST00000377371.3 linkuse as main transcript	c.421A>G	p.Lys141Glu	missense_variant	3/13	1		ENSP00000366588.3	Q504Y0-4
SLC39A12	ENST00000377374.8 linkuse as main transcript	c.421A>G	p.Lys141Glu	missense_variant	3/12	2		ENSP00000366591.4	Q504Y0-3
SLC39A12	ENST00000539911.5 linkuse as main transcript	c.19A>G	p.Lys7Glu	missense_variant	2/12	2		ENSP00000440445.1	Q504Y0-5

Frequencies

GnomAD3 genomes

AF:

0.0000920

AC:

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000851

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:

0.000108

AC:

AN:

251102

Hom.:

AF XY:

0.0000663

AC XY:

AN XY:

135716

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000347

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000115

Gnomad OTH exome

AF:

0.000327

GnomAD4 exome

AF:

0.0000438

AC:

AN:

1461814

Hom.:

Cov.:

AF XY:

0.0000454

AC XY:

AN XY:

727216

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000313

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:

0.0000405

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000920

AC:

AN:

152174

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000851

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

Alfa

AF:

0.0000847

Hom.:

Bravo

AF:

0.0000718

ExAC

AF:

0.0000988

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.000237

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

Aug 14, 2024

The c.421A>G (p.K141E) alteration is located in exon 3 (coding exon 2) of the SLC39A12 gene. This alteration results from a A to G substitution at nucleotide position 421, causing the lysine (K) at amino acid position 141 to be replaced by a glutamic acid (E). 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

0.080

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.61

CADD

Benign

8.8

DANN

Benign

0.90

DEOGEN2

Benign

0.0026

.;T;.;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.080

LIST_S2

Benign

0.67

T;T;T;T

M_CAP

Benign

0.015

MetaRNN

Benign

0.022

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

.;L;L;L

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.12

N;N;N;N

REVEL

Benign

0.021

Sift

Benign

0.25

T;T;T;T

Sift4G

Benign

0.71

T;T;T;T

Polyphen

0.0

.;B;B;B

Vest4

0.11

MutPred

0.32

.;Loss of methylation at K141 (P = 0.0098);Loss of methylation at K141 (P = 0.0098);Loss of methylation at K141 (P = 0.0098);

MVP

0.048

MPC

0.027

ClinPred

0.027

GERP RS

-4.5

Varity_R

0.048

gMVP

0.25

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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