Variant 18-36116710-G-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_012319.4(SLC39A6):c.1429C>G(p.Leu477Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000548 in 1,460,594 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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: 0.0000055 ( 0 hom. )

Consequence

SLC39A6
NM_012319.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.07

Variant links:

Genes affected

SLC39A6 (HGNC:18607): (solute carrier family 39 member 6) 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. SLC39A6 belongs to a subfamily of proteins that show structural characteristics of zinc transporters (Taylor and Nicholson, 2003 [PubMed 12659941]).[supplied by OMIM, Mar 2008]

SLC39A6 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=0.16438225).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC39A6	NM_012319.4 linkuse as main transcript	c.1429C>G	p.Leu477Val	missense_variant	6/10	ENST00000269187.10	NP_036451.4	Q13433-1
SLC39A6	NM_001099406.2 linkuse as main transcript	c.604C>G	p.Leu202Val	missense_variant	5/8		NP_001092876.1	Q13433-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SLC39A6	ENST00000269187.10 linkuse as main transcript	c.1429C>G	p.Leu477Val	missense_variant	6/10	2	NM_012319.4	ENSP00000269187.4	Q13433-1
SLC39A6	ENST00000440549.6 linkuse as main transcript	c.604C>G	p.Leu202Val	missense_variant	5/8	1		ENSP00000401139.1	Q13433-2
SLC39A6	ENST00000590986.5 linkuse as main transcript	c.1429C>G	p.Leu477Val	missense_variant	6/10	5		ENSP00000465915.1	Q13433-1
SLC39A6	ENST00000586829.1 linkuse as main transcript	c.130C>G	p.Leu44Val	missense_variant	2/5	3		ENSP00000467724.1	K7EQ91

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000805

AC:

AN:

248476

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134852

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:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000548

AC:

AN:

1460594

Hom.:

Cov.:

AF XY:

0.00000551

AC XY:

AN XY:

726602

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:

0.00000720

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.000111

Hom.:

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

Feb 06, 2023

The c.1429C>G (p.L477V) alteration is located in exon 6 (coding exon 5) of the SLC39A6 gene. This alteration results from a C to G substitution at nucleotide position 1429, causing the leucine (L) at amino acid position 477 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

0.066

BayesDel_addAF

Benign

-0.036

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.019

T;T;.;.

Eigen

Benign

-0.0053

Eigen_PC

Benign

0.19

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.79

.;T;T;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.16

T;T;T;T

MetaSVM

Benign

-0.79

MutationAssessor

Uncertain

2.3

M;M;.;.

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-0.31

N;.;N;.

REVEL

Benign

0.063

Sift

Benign

0.61

T;.;T;.

Sift4G

Benign

0.51

T;T;T;T

Polyphen

0.098

B;B;B;.

Vest4

0.28

MutPred

0.28

Gain of phosphorylation at Y473 (P = 0.2287);Gain of phosphorylation at Y473 (P = 0.2287);.;.;

MVP

0.76

MPC

0.13

ClinPred

0.30

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.086

gMVP

0.24

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