dbSNP rs375148755: SLC39A12:p.Leu16Ile (chr10-17953322-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_001145195.2(SLC39A12):c.46C>A(p.Leu16Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000167 in 1,614,096 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

SLC39A12
NM_001145195.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.775

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:

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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=0.07555848).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC39A12	NM_001145195.2 link	c.46C>A	p.Leu16Ile	missense_variant	Exon 2 of 13	ENST00000377369.7	NP_001138667.1	Q504Y0-1
SLC39A12	NM_001282733.2 link	c.46C>A	p.Leu16Ile	missense_variant	Exon 2 of 13		NP_001269662.1	Q504Y0-4
SLC39A12	NM_152725.4 link	c.46C>A	p.Leu16Ile	missense_variant	Exon 2 of 12		NP_689938.2	Q504Y0-3
SLC39A12	NM_001282734.2 link	c.-142+1297C>A		intron_variant	Intron 1 of 11		NP_001269663.1	Q504Y0-5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC39A12	ENST00000377369.7 link	c.46C>A	p.Leu16Ile	missense_variant	Exon 2 of 13	1	NM_001145195.2	ENSP00000366586.2	Q504Y0-1
SLC39A12	ENST00000377371.3 link	c.46C>A	p.Leu16Ile	missense_variant	Exon 2 of 13	1		ENSP00000366588.3	Q504Y0-4
SLC39A12	ENST00000377374.8 link	c.46C>A	p.Leu16Ile	missense_variant	Exon 2 of 12	2		ENSP00000366591.4	Q504Y0-3
SLC39A12	ENST00000539911.5 link	c.-142+1297C>A		intron_variant	Intron 1 of 11	2		ENSP00000440445.1	Q504Y0-5

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000164

AC:

AN:

1461894

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

727248

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:

0.0000207

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152202

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000225

Hom.:

Bravo

AF:

0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.55

CADD

Benign

6.5

DANN

Benign

0.93

DEOGEN2

Benign

0.0042

T;.;.

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.62

T;T;T

M_CAP

Benign

0.0061

MetaRNN

Benign

0.076

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.2

M;M;M

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.55

N;N;N

REVEL

Benign

0.022

Sift

Benign

0.16

T;T;T

Sift4G

Benign

0.14

T;T;T

Polyphen

0.069

B;B;B

Vest4

0.23

MutPred

0.21

Loss of disorder (P = 0.0659);Loss of disorder (P = 0.0659);Loss of disorder (P = 0.0659);

MVP

0.040

MPC

0.025

ClinPred

0.20

GERP RS

1.9

Varity_R

0.045

gMVP

0.24

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over