Variant chr18-36114169-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_012319.4(SLC39A6):c.1771G>A(p.Gly591Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000958 in 1,461,862 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

SLC39A6
NM_012319.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.15

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC39A6	NM_012319.4 linkuse as main transcript	c.1771G>A	p.Gly591Ser	missense_variant	7/10	ENST00000269187.10	NP_036451.4	Q13433-1
SLC39A6	NM_001099406.2 linkuse as main transcript	c.946G>A	p.Gly316Ser	missense_variant	6/8		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.1771G>A	p.Gly591Ser	missense_variant	7/10	2	NM_012319.4	ENSP00000269187.4	Q13433-1
SLC39A6	ENST00000440549.6 linkuse as main transcript	c.946G>A	p.Gly316Ser	missense_variant	6/8	1		ENSP00000401139.1	Q13433-2
SLC39A6	ENST00000590986.5 linkuse as main transcript	c.1771G>A	p.Gly591Ser	missense_variant	7/10	5		ENSP00000465915.1	Q13433-1
SLC39A6	ENST00000586829.1 linkuse as main transcript	c.472G>A	p.Gly158Ser	missense_variant	3/5	3		ENSP00000467724.1	K7EQ91

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000405

AC:

AN:

247174

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134298

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

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:

0.00000958

AC:

AN:

1461862

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000899

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000986

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.00000825

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 27, 2022

The c.1771G>A (p.G591S) alteration is located in exon 7 (coding exon 6) of the SLC39A6 gene. This alteration results from a G to A substitution at nucleotide position 1771, causing the glycine (G) at amino acid position 591 to be replaced by a serine (S). 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

0.32

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Uncertain

-0.040

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.20

T;T;.;.

Eigen

Uncertain

0.62

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.93

.;D;D;D

M_CAP

Benign

0.039

MetaRNN

Uncertain

0.59

D;D;D;D

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.9

L;L;.;.

PrimateAI

Uncertain

0.73

PROVEAN

Uncertain

-3.2

D;.;D;.

REVEL

Uncertain

0.34

Sift

Pathogenic

0.0

D;.;T;.

Sift4G

Pathogenic

0.0

D;D;T;T

Polyphen

1.0

D;D;D;.

Vest4

0.41

MutPred

0.56

Loss of catalytic residue at G591 (P = 0.039);Loss of catalytic residue at G591 (P = 0.039);.;.;

MVP

0.53

MPC

2.1

ClinPred

0.94

GERP RS

6.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.61

gMVP

0.86

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