1-153960346-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001271958.2(SLC39A1):​c.727G>A​(p.Gly243Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

SLC39A1
NM_001271958.2 missense

Scores

3
8
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.15
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.773

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC39A1NM_001271958.2 linkc.727G>A p.Gly243Arg missense_variant Exon 4 of 4 ENST00000356205.9 NP_001258887.1 Q9NY26-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC39A1ENST00000356205.9 linkc.727G>A p.Gly243Arg missense_variant Exon 4 of 4 1 NM_001271958.2 ENSP00000348535.4 Q9NY26-1
ENSG00000285779ENST00000648921.1 linkn.*815G>A non_coding_transcript_exon_variant Exon 6 of 6 ENSP00000498105.1 A0A3B3ITX8
ENSG00000285779ENST00000648921.1 linkn.*815G>A 3_prime_UTR_variant Exon 6 of 6 ENSP00000498105.1 A0A3B3ITX8

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 13, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.727G>A (p.G243R) alteration is located in exon 5 (coding exon 3) of the SLC39A1 gene. This alteration results from a G to A substitution at nucleotide position 727, causing the glycine (G) at amino acid position 243 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
0.97
BayesDel_addAF
Pathogenic
0.17
D
BayesDel_noAF
Uncertain
0.0
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.40
T;T;T;T;T;T;.
Eigen
Uncertain
0.23
Eigen_PC
Uncertain
0.27
FATHMM_MKL
Uncertain
0.78
D
LIST_S2
Uncertain
0.88
.;.;D;.;.;.;D
M_CAP
Benign
0.017
T
MetaRNN
Pathogenic
0.77
D;D;D;D;D;D;D
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.4
L;L;L;L;L;L;.
PrimateAI
Uncertain
0.64
T
PROVEAN
Benign
-0.21
.;N;.;N;N;N;N
REVEL
Benign
0.23
Sift
Uncertain
0.021
.;D;.;D;D;D;D
Sift4G
Benign
0.17
T;T;T;T;T;T;T
Polyphen
0.81
P;P;P;P;P;P;.
Vest4
0.54
MutPred
0.84
Gain of methylation at G243 (P = 0.0235);Gain of methylation at G243 (P = 0.0235);Gain of methylation at G243 (P = 0.0235);Gain of methylation at G243 (P = 0.0235);Gain of methylation at G243 (P = 0.0235);Gain of methylation at G243 (P = 0.0235);Gain of methylation at G243 (P = 0.0235);
MVP
0.62
MPC
0.54
ClinPred
0.69
D
GERP RS
4.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.16
gMVP
0.82

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-153932822; API