dbSNP rs140376410: SLC39A3:p.Arg169Leu (chr19-2733190-C-A) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_144564.5(SLC39A3):c.506G>T(p.Arg169Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,292 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R169H) has been classified as Benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

SLC39A3
NM_144564.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.39

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.87

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC39A3	NM_144564.5 link	c.506G>T	p.Arg169Leu	missense_variant	Exon 3 of 3	ENST00000269740.9	NP_653165.2	Q9BRY0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC39A3	ENST00000269740.9 link	c.506G>T	p.Arg169Leu	missense_variant	Exon 3 of 3	1	NM_144564.5	ENSP00000269740.3		Q9BRY0-1
ENSG00000267001	ENST00000586572.1 link	c.210+3858G>T		intron_variant	Intron 2 of 2	4		ENSP00000467958.1		K7EQS6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000434

AC:

AN:

230422

Hom.:

AF XY:

0.00

AC XY:

AN XY:

127380

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:

0.0000473

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1455292

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

723736

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

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

Cov.:

ExAC

AF:

0.00000845

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.46

BayesDel_addAF

Pathogenic

0.22

BayesDel_noAF

Uncertain

0.080

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.38

.;T

Eigen

Uncertain

0.67

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.86

D;D

M_CAP

Benign

0.041

MetaRNN

Pathogenic

0.87

D;D

MetaSVM

Benign

-0.42

MutationAssessor

Pathogenic

3.0

.;M

PrimateAI

Pathogenic

0.82

PROVEAN

Uncertain

-4.2

D;D

REVEL

Uncertain

0.44

Sift

Uncertain

0.0050

D;D

Sift4G

Uncertain

0.0060

D;D

Polyphen

1.0

D;D

Vest4

0.88

MutPred

0.60

Loss of disorder (P = 0.0603);Loss of disorder (P = 0.0603);

MVP

0.72

MPC

1.2

ClinPred

0.99

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.56

gMVP

0.89

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over