14-69458502-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018375.5(SLC39A9):​c.833C>T​(p.Thr278Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000297 in 1,614,252 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000026 ( 1 hom. )

Consequence

SLC39A9
NM_018375.5 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0780
Variant links:
Genes affected
SLC39A9 (HGNC:20182): (solute carrier family 39 member 9) Predicted to enable metal ion transmembrane transporter activity. Predicted to be involved in transmembrane transport and zinc ion transport. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

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=0.0725044).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC39A9NM_018375.5 linkc.833C>T p.Thr278Met missense_variant Exon 7 of 7 ENST00000336643.10 NP_060845.2 Q9NUM3-1C4N9M8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC39A9ENST00000336643.10 linkc.833C>T p.Thr278Met missense_variant Exon 7 of 7 1 NM_018375.5 ENSP00000336887.5 Q9NUM3-1

Frequencies

GnomAD3 genomes
AF:
0.0000657
AC:
10
AN:
152244
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000965
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:
0.0000882
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000398
AC:
10
AN:
251390
Hom.:
0
AF XY:
0.0000368
AC XY:
5
AN XY:
135870
show subpopulations
Gnomad AFR exome
AF:
0.000123
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:
0.0000616
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.0000260
AC:
38
AN:
1461890
Hom.:
1
Cov.:
32
AF XY:
0.0000289
AC XY:
21
AN XY:
727246
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.000191
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000261
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.0000656
AC:
10
AN:
152362
Hom.:
0
Cov.:
32
AF XY:
0.0000671
AC XY:
5
AN XY:
74502
show subpopulations
Gnomad4 AFR
AF:
0.0000962
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:
0.0000882
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000792
Hom.:
0
Bravo
AF:
0.0000756
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000576
AC:
7
EpiCase
AF:
0.0000545
EpiControl
AF:
0.0000593

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Dec 25, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.833C>T (p.T278M) alteration is located in exon 7 (coding exon 7) of the SLC39A9 gene. This alteration results from a C to T substitution at nucleotide position 833, causing the threonine (T) at amino acid position 278 to be replaced by a methionine (M). 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
Benign
0.095
BayesDel_addAF
Benign
-0.32
T
BayesDel_noAF
Benign
-0.46
CADD
Benign
16
DANN
Benign
0.95
DEOGEN2
Benign
0.018
T;.;.
Eigen
Benign
-0.86
Eigen_PC
Benign
-0.95
FATHMM_MKL
Benign
0.14
N
LIST_S2
Uncertain
0.92
.;D;D
M_CAP
Benign
0.030
D
MetaRNN
Benign
0.073
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.2
L;.;.
PrimateAI
Benign
0.29
T
PROVEAN
Benign
-2.0
N;.;N
REVEL
Benign
0.13
Sift
Benign
0.059
T;.;T
Sift4G
Uncertain
0.031
D;T;T
Polyphen
0.70
P;.;B
Vest4
0.19
MVP
0.11
MPC
1.1
ClinPred
0.025
T
GERP RS
0.46
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.021
gMVP
0.36

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs200562708; hg19: chr14-69925219; COSMIC: COSV50362184; API