chr18-36116676-T-C

Position:

chr18-36116676-T-C

Variant summary

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

The NM_012319.4(SLC39A6):c.1463A>G(p.Asp488Gly) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000187 in 1,601,370 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

SLC39A6
NM_012319.4 missense, splice_region

Scores

Splicing: ADA: 0.1232

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.59

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:

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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=0.17049426).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC39A6	NM_012319.4 linkuse as main transcript	c.1463A>G	p.Asp488Gly	missense_variant, splice_region_variant	6/10	ENST00000269187.10	NP_036451.4	Q13433-1
SLC39A6	NM_001099406.2 linkuse as main transcript	c.638A>G	p.Asp213Gly	missense_variant, splice_region_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.1463A>G	p.Asp488Gly	missense_variant, splice_region_variant	6/10	2	NM_012319.4	ENSP00000269187.4	Q13433-1
SLC39A6	ENST00000440549.6 linkuse as main transcript	c.638A>G	p.Asp213Gly	missense_variant, splice_region_variant	5/8	1		ENSP00000401139.1	Q13433-2
SLC39A6	ENST00000590986.5 linkuse as main transcript	c.1463A>G	p.Asp488Gly	missense_variant, splice_region_variant	6/10	5		ENSP00000465915.1	Q13433-1
SLC39A6	ENST00000586829.1 linkuse as main transcript	c.164A>G	p.Asp55Gly	missense_variant, splice_region_variant	2/5	3		ENSP00000467724.1	K7EQ91

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152106

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000806

AC:

AN:

248082

Hom.:

AF XY:

0.00000743

AC XY:

AN XY:

134610

show subpopulations

Gnomad AFR exome

AF:

0.000130

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.90e-7

AC:

AN:

1449264

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

721684

show subpopulations

Gnomad4 AFR exome

AF:

0.0000301

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152106

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74328

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.0000165

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

Jan 08, 2024

The c.1463A>G (p.D488G) alteration is located in exon 6 (coding exon 5) of the SLC39A6 gene. This alteration results from a A to G substitution at nucleotide position 1463, causing the aspartic acid (D) at amino acid position 488 to be replaced by a glycine (G). 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

-0.25

BayesDel_noAF

Benign

-0.37

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.060

T;T;.;.

Eigen

Benign

0.034

Eigen_PC

Benign

0.20

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.76

.;T;T;T

M_CAP

Benign

0.0096

MetaRNN

Benign

0.17

T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.0

N;N;.;.

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.9

N;.;N;.

REVEL

Benign

0.056

Sift

Uncertain

0.028

D;.;D;.

Sift4G

Benign

0.20

T;T;T;T

Polyphen

0.38

B;B;B;.

Vest4

0.26

MutPred

0.28

Loss of helix (P = 0.0626);Loss of helix (P = 0.0626);.;.;

MVP

0.58

MPC

0.23

ClinPred

0.23

GERP RS

5.2

Varity_R

0.21

gMVP

0.34

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.12

dbscSNV1_RF

Benign

0.37

SpliceAI score (max)

0.16

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