chr12-56231330-T-C
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_173596.3(SLC39A5):c.56T>C(p.Leu19Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00644 in 1,613,412 control chromosomes in the GnomAD database, including 50 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0043 ( 2 hom., cov: 32)
Exomes 𝑓: 0.0067 ( 48 hom. )
Consequence
SLC39A5
NM_173596.3 missense
NM_173596.3 missense
Scores
1
15
Clinical Significance
Conservation
PhyloP100: 2.57
Genes affected
SLC39A5 (HGNC:20502): (solute carrier family 39 member 5) The protein encoded by this gene belongs to the ZIP family of zinc transporters that transport zinc into cells from outside, and play a crucial role in controlling intracellular zinc levels. Zinc is an essential cofactor for many enzymes and proteins involved in gene transcription, growth, development and differentiation. Mutations in this gene have been associated with autosomal dominant high myopia (MYP24). Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2014]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.006154835).
BP6
?
Variant 12-56231330-T-C is Benign according to our data. Variant chr12-56231330-T-C is described in ClinVar as [Benign]. Clinvar id is 768554.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-56231330-T-C is described in Lovd as [Likely_benign].
BS2
?
High AC in GnomAd at 657 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC39A5 | NM_173596.3 | c.56T>C | p.Leu19Ser | missense_variant | 4/13 | ENST00000454355.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC39A5 | ENST00000454355.7 | c.56T>C | p.Leu19Ser | missense_variant | 4/13 | 1 | NM_173596.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00432 AC: 657AN: 152130Hom.: 2 Cov.: 32
GnomAD3 genomes
?
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657
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152130
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32
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GnomAD3 exomes AF: 0.00549 AC: 1370AN: 249382Hom.: 11 AF XY: 0.00591 AC XY: 798AN XY: 135112
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GnomAD4 exome AF: 0.00666 AC: 9726AN: 1461164Hom.: 48 Cov.: 34 AF XY: 0.00674 AC XY: 4896AN XY: 726898
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GnomAD4 genome ? AF: 0.00432 AC: 657AN: 152248Hom.: 2 Cov.: 32 AF XY: 0.00449 AC XY: 334AN XY: 74444
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657
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ESP6500AA
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ESP6500EA
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63
ExAC
?
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664
Asia WGS
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7
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3478
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Aug 24, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2022 | SLC39A5: BP4, BS1, BS2 - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;.;T;T;T
MetaRNN
Benign
T;T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N;N;N;N
REVEL
Benign
Sift
Benign
T;T;T;T;T;T
Sift4G
Benign
T;T;T;T;T;T
Polyphen
0.0060
.;.;B;.;B;.
Vest4
0.48, 0.49
MVP
MPC
0.17
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at