Variant 1-153960358-C-A 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_001271958.2(SLC39A1):c.715G>T(p.Val239Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,638 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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: 0.0000014 ( 0 hom. )

Consequence

SLC39A1
NM_001271958.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.29

Variant links:

Genes affected

SLC39A1 (HGNC:12876): (solute carrier family 39 member 1) This gene encodes a member of the zinc-iron permease family. The encoded protein is localized to the cell membrane and acts as a zinc uptake transporter. This gene has been linked to prostate cancer, breast cancer, and Alzheimer's disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2012]

SLC39A1 links:

ENSG00000285779 (HGNC:):

ENSG00000285779 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=0.22268516).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC39A1	NM_001271958.2 linkuse as main transcript	c.715G>T	p.Val239Leu	missense_variant	4/4	ENST00000356205.9	NP_001258887.1	Q9NY26-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SLC39A1	ENST00000356205.9 linkuse as main transcript	c.715G>T	p.Val239Leu	missense_variant	4/4	1	NM_001271958.2	ENSP00000348535.4	Q9NY26-1
ENSG00000285779	ENST00000648921.1 linkuse as main transcript	n.*803G>T		non_coding_transcript_exon_variant	6/6			ENSP00000498105.1	A0A3B3ITX8
ENSG00000285779	ENST00000648921.1 linkuse as main transcript	n.*803G>T		3_prime_UTR_variant	6/6			ENSP00000498105.1	A0A3B3ITX8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000400

AC:

AN:

250156

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135458

show subpopulations

Gnomad AFR exome

AF:

0.0000619

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:

0.00000137

AC:

AN:

1461638

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727120

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

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.:

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 05, 2022

The c.715G>T (p.V239L) alteration is located in exon 5 (coding exon 3) of the SLC39A1 gene. This alteration results from a G to T substitution at nucleotide position 715, causing the valine (V) at amino acid position 239 to be replaced by a leucine (L). 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

Uncertain

0.47

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.16

T;T;T;T;T;T;.;.

Eigen

Benign

-0.099

Eigen_PC

Benign

0.025

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.80

.;.;T;.;.;.;T;T

M_CAP

Benign

0.0072

MetaRNN

Benign

0.22

T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.43

N;N;N;N;N;N;.;.

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-0.90

.;N;.;N;N;N;N;N

REVEL

Benign

0.18

Sift

Benign

0.14

.;T;.;T;T;T;T;D

Sift4G

Benign

0.21

T;T;T;T;T;T;T;D

Polyphen

0.060

B;B;B;B;B;B;.;.

Vest4

0.11

MutPred

0.66

Gain of methylation at R235 (P = 0.1531);Gain of methylation at R235 (P = 0.1531);Gain of methylation at R235 (P = 0.1531);Gain of methylation at R235 (P = 0.1531);Gain of methylation at R235 (P = 0.1531);Gain of methylation at R235 (P = 0.1531);Gain of methylation at R235 (P = 0.1531);Gain of methylation at R235 (P = 0.1531);

MVP

0.53

MPC

0.42

ClinPred

0.15

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.11

gMVP

0.61

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