chr10-17987607-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001145195.2(SLC39A12):c.1225G>A(p.Val409Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000328 in 1,614,026 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000034 ( 0 hom. )
Consequence
SLC39A12
NM_001145195.2 missense
NM_001145195.2 missense
Scores
1
5
11
Clinical Significance
Conservation
PhyloP100: 7.50
Genes affected
SLC39A12 (HGNC:20860): (solute carrier family 39 member 12) Zinc is an essential cofactor for hundreds of enzymes. It is involved in protein, nucleic acid, carbohydrate, and lipid metabolism, as well as in the control of gene transcription, growth, development, and differentiation. SLC39A12 belongs to a subfamily of proteins that show structural characteristics of zinc transporters (Taylor and Nicholson, 2003 [PubMed 12659941]).[supplied by OMIM, Aug 2008]
Genome browser will be placed here
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 | UniProt |
---|---|---|---|---|---|---|---|
SLC39A12 | NM_001145195.2 | c.1225G>A | p.Val409Ile | missense_variant | 7/13 | ENST00000377369.7 | |
SLC39A12 | NM_001282733.2 | c.1225G>A | p.Val409Ile | missense_variant | 7/13 | ||
SLC39A12 | NM_152725.4 | c.1225G>A | p.Val409Ile | missense_variant | 7/12 | ||
SLC39A12 | NM_001282734.2 | c.823G>A | p.Val275Ile | missense_variant | 6/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC39A12 | ENST00000377369.7 | c.1225G>A | p.Val409Ile | missense_variant | 7/13 | 1 | NM_001145195.2 | A1 | |
SLC39A12 | ENST00000377371.3 | c.1225G>A | p.Val409Ile | missense_variant | 7/13 | 1 | P4 | ||
SLC39A12 | ENST00000377374.8 | c.1225G>A | p.Val409Ile | missense_variant | 7/12 | 2 | |||
SLC39A12 | ENST00000539911.5 | c.823G>A | p.Val275Ile | missense_variant | 6/12 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152152Hom.: 0 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
4
AN:
152152
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000318 AC: 8AN: 251464Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135906
GnomAD3 exomes
AF:
AC:
8
AN:
251464
Hom.:
AF XY:
AC XY:
5
AN XY:
135906
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000335 AC: 49AN: 1461874Hom.: 0 Cov.: 31 AF XY: 0.0000316 AC XY: 23AN XY: 727240
GnomAD4 exome
AF:
AC:
49
AN:
1461874
Hom.:
Cov.:
31
AF XY:
AC XY:
23
AN XY:
727240
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152152Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74328
GnomAD4 genome
?
AF:
AC:
4
AN:
152152
Hom.:
Cov.:
32
AF XY:
AC XY:
2
AN XY:
74328
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ESP6500AA
AF:
AC:
0
ESP6500EA
AF:
AC:
1
ExAC
?
AF:
AC:
7
EpiCase
AF:
EpiControl
AF:
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 | Jun 06, 2023 | The c.1225G>A (p.V409I) alteration is located in exon 7 (coding exon 6) of the SLC39A12 gene. This alteration results from a G to A substitution at nucleotide position 1225, causing the valine (V) at amino acid position 409 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D
M_CAP
Benign
T
MetaRNN
Uncertain
D;D;D;D
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N;N
REVEL
Benign
Sift
Benign
D;D;T;T
Sift4G
Benign
T;T;T;T
Polyphen
0.97, 0.98, 0.98
.;D;D;D
Vest4
MVP
MPC
0.16
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at