Menu
GeneBe

1-153960322-G-A

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_001271958.2(SLC39A1):c.751C>T(p.Pro251Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000123 in 1,461,690 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

SLC39A1
NM_001271958.2 missense

Scores

7
5
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.94
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 Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.968

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SLC39A1NM_001271958.2 linkuse as main transcriptc.751C>T p.Pro251Ser missense_variant 4/4 ENST00000356205.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SLC39A1ENST00000356205.9 linkuse as main transcriptc.751C>T p.Pro251Ser missense_variant 4/41 NM_001271958.2 P1Q9NY26-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000798
AC:
2
AN:
250704
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135688
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:
0.0000177
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000123
AC:
18
AN:
1461690
Hom.:
0
Cov.:
31
AF XY:
0.0000151
AC XY:
11
AN XY:
727152
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:
0.0000188
Gnomad4 NFE exome
AF:
0.0000153
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Alfa
AF:
0.0000282
Hom.:
0
Bravo
AF:
0.00000756
ExAC
AF:
0.0000165
AC:
2
EpiCase
AF:
0.0000545
EpiControl
AF:
0.000178

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 submitterclinical testingAmbry GeneticsJan 31, 2023The c.751C>T (p.P251S) alteration is located in exon 5 (coding exon 3) of the SLC39A1 gene. This alteration results from a C to T substitution at nucleotide position 751, causing the proline (P) at amino acid position 251 to be replaced by a serine (S). 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
0.94
BayesDel_addAF
Pathogenic
0.32
D
BayesDel_noAF
Pathogenic
0.22
Cadd
Pathogenic
28
Dann
Uncertain
1.0
DEOGEN2
Uncertain
0.59
D;D;D;D;D;D;.
Eigen
Pathogenic
0.71
Eigen_PC
Uncertain
0.66
FATHMM_MKL
Pathogenic
0.97
D
M_CAP
Benign
0.063
D
MetaRNN
Pathogenic
0.97
D;D;D;D;D;D;D
MetaSVM
Benign
-0.46
T
MutationAssessor
Uncertain
2.8
M;M;M;M;M;M;.
MutationTaster
Benign
1.0
D;D;D;D;D
PrimateAI
Uncertain
0.74
T
Sift4G
Pathogenic
0.0
D;D;D;D;D;D;D
Polyphen
1.0
D;D;D;D;D;D;.
Vest4
0.81
MutPred
0.92
Gain of helix (P = 0.2294);Gain of helix (P = 0.2294);Gain of helix (P = 0.2294);Gain of helix (P = 0.2294);Gain of helix (P = 0.2294);Gain of helix (P = 0.2294);Gain of helix (P = 0.2294);
MVP
0.85
MPC
1.0
ClinPred
1.0
D
GERP RS
4.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.81
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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs754542240; hg19: chr1-153932798; API