Variant chr1-153960532-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001271958.2(SLC39A1):c.541T>C(p.Cys181Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,613,768 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

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

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SLC39A1
NM_001271958.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.10

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 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
SLC39A1	NM_001271958.2 linkuse as main transcript	c.541T>C	p.Cys181Arg	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.541T>C	p.Cys181Arg	missense_variant	4/4	1	NM_001271958.2	ENSP00000348535.4	Q9NY26-1
ENSG00000285779	ENST00000648921.1 linkuse as main transcript	n.*629T>C		non_coding_transcript_exon_variant	6/6			ENSP00000498105.1	A0A3B3ITX8
ENSG00000285779	ENST00000648921.1 linkuse as main transcript	n.*629T>C		3_prime_UTR_variant	6/6			ENSP00000498105.1	A0A3B3ITX8

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152264

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250692

Hom.:

AF XY:

0.00000738

AC XY:

AN XY:

135564

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:

0.00

Gnomad NFE exome

AF:

0.00000882

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461504

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727048

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152264

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

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 26, 2022

The c.541T>C (p.C181R) alteration is located in exon 5 (coding exon 3) of the SLC39A1 gene. This alteration results from a T to C substitution at nucleotide position 541, causing the cysteine (C) at amino acid position 181 to be replaced by an arginine (R). 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

Pathogenic

0.95

BayesDel_addAF

Uncertain

0.022

BayesDel_noAF

Benign

-0.21

CADD

Uncertain

DANN

Benign

0.63

DEOGEN2

Benign

0.16

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

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.30

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.78

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

M_CAP

Benign

0.0091

MetaRNN

Uncertain

0.52

D;D;D;D;D;D;D;D;D

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.90

L;L;L;L;L;L;.;.;.

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-1.7

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

REVEL

Benign

0.24

Sift

Benign

0.31

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

Sift4G

Benign

0.32

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

Polyphen

0.037

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

Vest4

0.50

MutPred

0.88

Gain of methylation at C181 (P = 0.0189);Gain of methylation at C181 (P = 0.0189);Gain of methylation at C181 (P = 0.0189);Gain of methylation at C181 (P = 0.0189);Gain of methylation at C181 (P = 0.0189);Gain of methylation at C181 (P = 0.0189);Gain of methylation at C181 (P = 0.0189);Gain of methylation at C181 (P = 0.0189);Gain of methylation at C181 (P = 0.0189);

MVP

0.40

MPC

0.56

ClinPred

0.089

GERP RS

3.6

Varity_R

0.34

gMVP

0.56

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