Genetic Variant SLC39A3:p.Val206Ile (chr19-2733080-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_144564.5(SLC39A3):c.616G>A(p.Val206Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000584 in 1,610,514 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000046 ( 0 hom. )

Consequence

SLC39A3
NM_144564.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.750

Publications

1 publications found

Variant links:

Genes affected

SLC39A3 (HGNC:17128): (solute carrier family 39 member 3) Predicted to enable zinc ion transmembrane transporter activity. Predicted to be involved in zinc ion transmembrane transport. Predicted to act upstream of or within several processes, including T cell homeostasis; chordate embryonic development; and zinc ion transport. Predicted to be integral component of membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC39A3 links:

ENSG00000267001 (HGNC:):

ENSG00000267001 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.040236115).

BP6

Variant 19-2733080-C-T is Benign according to our data. Variant chr19-2733080-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3444415.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144564.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC39A3	NM_144564.5	MANE Select	c.616G>A	p.Val206Ile	missense	Exon 3 of 3	NP_653165.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC39A3	ENST00000269740.9	TSL:1 MANE Select	c.616G>A	p.Val206Ile	missense	Exon 3 of 3	ENSP00000269740.3	Q9BRY0-1
ENSG00000267001	ENST00000586572.1	TSL:4	c.210+3968G>A		intron	N/A	ENSP00000467958.1	K7EQS6
SLC39A3	ENST00000545664.5	TSL:2	c.616G>A	p.Val206Ile	missense	Exon 3 of 4	ENSP00000445345.1	F5H385

Frequencies

GnomAD3 genomes

AF:

0.000178

AC:

AN:

152074

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000765

AC:

AN:

235344

AF XY:

0.000116

show subpopulations

Gnomad AFR exome

AF:

0.000139

Gnomad AMR exome

AF:

0.000147

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000587

Gnomad OTH exome

AF:

0.000172

GnomAD4 exome

AF:

0.0000459

AC:

AN:

1458324

Hom.:

Cov.:

AF XY:

0.0000593

AC XY:

AN XY:

725406

show subpopulations

African (AFR)

AF:

0.000120

AC:

AN:

33334

American (AMR)

AF:

0.000157

AC:

AN:

44562

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26030

East Asian (EAS)

AF:

0.00

AC:

AN:

39632

South Asian (SAS)

AF:

0.0000930

AC:

AN:

86064

European-Finnish (FIN)

AF:

0.0000193

AC:

AN:

51802

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.0000360

AC:

AN:

1110884

Other (OTH)

AF:

0.0000996

AC:

AN:

60260

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000177

AC:

AN:

152190

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74412

show subpopulations

African (AFR)

AF:

0.000193

AC:

AN:

41542

American (AMR)

AF:

0.00111

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5152

South Asian (SAS)

AF:

0.000207

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67966

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.000193

ESP6500AA

AF:

0.000233

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000668

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3472

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.27

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.039

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.095

LIST_S2

Benign

0.79

M_CAP

Benign

0.0071

MetaRNN

Benign

0.040

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-0.23

PhyloP100

-0.75

PrimateAI

Benign

0.38

PROVEAN

Benign

0.47

REVEL

Benign

0.087

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0010

Vest4

0.15

MVP

0.25

MPC

0.26

ClinPred

0.0073

GERP RS

-4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.025

gMVP

0.12

Mutation Taster

=95/5

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over