chr10-17978031-C-T

Position:

chr10-17978031-C-T

Variant summary

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

The NM_001145195.2(SLC39A12):c.881C>T(p.Ser294Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000586 in 1,603,566 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: 𝑓 0.000053 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000059 ( 0 hom. )

Consequence

SLC39A12
NM_001145195.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0510

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 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=0.0922375).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SLC39A12	NM_001145195.2 linkuse as main transcript	c.881C>T	p.Ser294Phe	missense_variant	5/13	ENST00000377369.7	NP_001138667.1
SLC39A12	NM_001282733.2 linkuse as main transcript	c.881C>T	p.Ser294Phe	missense_variant	5/13		NP_001269662.1
SLC39A12	NM_152725.4 linkuse as main transcript	c.881C>T	p.Ser294Phe	missense_variant	5/12		NP_689938.2
SLC39A12	NM_001282734.2 linkuse as main transcript	c.479C>T	p.Ser160Phe	missense_variant	4/12		NP_001269663.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC39A12	ENST00000377369.7 linkuse as main transcript	c.881C>T	p.Ser294Phe	missense_variant	5/13	1	NM_001145195.2	ENSP00000366586	A1	Q504Y0-1
SLC39A12	ENST00000377371.3 linkuse as main transcript	c.881C>T	p.Ser294Phe	missense_variant	5/13	1		ENSP00000366588	P4	Q504Y0-4
SLC39A12	ENST00000377374.8 linkuse as main transcript	c.881C>T	p.Ser294Phe	missense_variant	5/12	2		ENSP00000366591		Q504Y0-3
SLC39A12	ENST00000539911.5 linkuse as main transcript	c.479C>T	p.Ser160Phe	missense_variant	4/12	2		ENSP00000440445		Q504Y0-5

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

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:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000166

AC:

AN:

241250

Hom.:

AF XY:

0.0000229

AC XY:

AN XY:

130764

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:

0.0000361

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000593

AC:

AN:

1451408

Hom.:

Cov.:

AF XY:

0.0000637

AC XY:

AN XY:

721948

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:

0.0000758

Gnomad4 OTH exome

AF:

0.0000333

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152158

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.0000483

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:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000141

Hom.:

Bravo

AF:

0.0000378

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000519

AC:

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 29, 2021

The c.881C>T (p.S294F) alteration is located in exon 5 (coding exon 4) of the SLC39A12 gene. This alteration results from a C to T substitution at nucleotide position 881, causing the serine (S) at amino acid position 294 to be replaced by a phenylalanine (F). 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

0.085

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.50

CADD

Benign

3.7

DANN

Benign

0.77

DEOGEN2

Benign

0.0065

.;T;.;.

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.90

FATHMM_MKL

Benign

0.039

LIST_S2

Benign

0.51

T;T;T;T

M_CAP

Benign

0.016

MetaRNN

Benign

0.092

T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.7

.;L;L;L

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.7

N;N;N;N

REVEL

Benign

0.10

Sift

Benign

0.22

T;T;T;T

Sift4G

Benign

0.10

T;T;T;T

Polyphen

0.0020, 0.019, 0.017

.;B;B;B

Vest4

0.15

MutPred

0.25

.;Loss of phosphorylation at S294 (P = 0.0276);Loss of phosphorylation at S294 (P = 0.0276);Loss of phosphorylation at S294 (P = 0.0276);

MVP

0.13

MPC

0.024

ClinPred

0.047

GERP RS

0.69

Varity_R

0.048

gMVP

0.32

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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