Genetic Variant SLC39A12:p.Met211Val (chr10-17965570-A-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

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

The NM_001145195.2(SLC39A12):c.631A>G(p.Met211Val) 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 1,461,868 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SLC39A12
NM_001145195.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.69

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 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=0.033325046).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC39A12	NM_001145195.2 link	c.631A>G	p.Met211Val	missense_variant	Exon 4 of 13	ENST00000377369.7	NP_001138667.1	Q504Y0-1
SLC39A12	NM_001282733.2 link	c.631A>G	p.Met211Val	missense_variant	Exon 4 of 13		NP_001269662.1	Q504Y0-4
SLC39A12	NM_152725.4 link	c.631A>G	p.Met211Val	missense_variant	Exon 4 of 12		NP_689938.2	Q504Y0-3
SLC39A12	NM_001282734.2 link	c.229A>G	p.Met77Val	missense_variant	Exon 3 of 12		NP_001269663.1	Q504Y0-5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC39A12	ENST00000377369.7 link	c.631A>G	p.Met211Val	missense_variant	Exon 4 of 13	1	NM_001145195.2	ENSP00000366586.2	Q504Y0-1
SLC39A12	ENST00000377371.3 link	c.631A>G	p.Met211Val	missense_variant	Exon 4 of 13	1		ENSP00000366588.3	Q504Y0-4
SLC39A12	ENST00000377374.8 link	c.631A>G	p.Met211Val	missense_variant	Exon 4 of 12	2		ENSP00000366591.4	Q504Y0-3
SLC39A12	ENST00000539911.5 link	c.229A>G	p.Met77Val	missense_variant	Exon 3 of 12	2		ENSP00000440445.1	Q504Y0-5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251482

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135912

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461868

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727236

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 27, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.631A>G (p.M211V) alteration is located in exon 4 (coding exon 3) of the SLC39A12 gene. This alteration results from a A to G substitution at nucleotide position 631, causing the methionine (M) at amino acid position 211 to be replaced by a valine (V). 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

0.090

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

6.0

DANN

Benign

0.34

DEOGEN2

Benign

0.00065

.;T;.;.

Eigen

Benign

-0.89

Eigen_PC

Benign

-0.80

FATHMM_MKL

Benign

0.075

LIST_S2

Benign

0.55

T;T;T;T

M_CAP

Benign

0.015

MetaRNN

Benign

0.033

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

.;L;L;L

PrimateAI

Benign

0.21

PROVEAN

Benign

0.17

N;N;N;N

REVEL

Benign

0.055

Sift

Benign

0.62

T;T;T;T

Sift4G

Benign

0.85

T;T;T;T

Polyphen

0.0, 0.0010

.;B;B;B

Vest4

0.10

MutPred

0.28

.;Gain of catalytic residue at M211 (P = 0.1083);Gain of catalytic residue at M211 (P = 0.1083);Gain of catalytic residue at M211 (P = 0.1083);

MVP

0.072

MPC

0.023

ClinPred

0.072

GERP RS

4.9

Varity_R

0.045

gMVP

0.32

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