12-56231284-T-C
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_173596.3(SLC39A5):c.10T>C(p.Ser4Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00129 in 1,605,402 control chromosomes in the GnomAD database, including 35 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 0.0071 ( 20 hom., cov: 32)
Exomes 𝑓: 0.00068 ( 15 hom. )
Consequence
SLC39A5
NM_173596.3 missense
NM_173596.3 missense
Scores
16
Clinical Significance
Conservation
PhyloP100: -1.40
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 -14 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0020042956).
BP6
?
Variant 12-56231284-T-C is Benign according to our data. Variant chr12-56231284-T-C is described in ClinVar as [Benign]. Clinvar id is 776719.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00713 (1084/152112) while in subpopulation AFR AF= 0.0248 (1029/41520). AF 95% confidence interval is 0.0235. There are 20 homozygotes in gnomad4. There are 539 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd at 1086 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC39A5 | NM_173596.3 | c.10T>C | p.Ser4Pro | missense_variant | 4/13 | ENST00000454355.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC39A5 | ENST00000454355.7 | c.10T>C | p.Ser4Pro | missense_variant | 4/13 | 1 | NM_173596.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00715 AC: 1086AN: 151994Hom.: 20 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.00174 AC: 421AN: 242598Hom.: 7 AF XY: 0.00128 AC XY: 168AN XY: 131744
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GnomAD4 exome AF: 0.000680 AC: 988AN: 1453290Hom.: 15 Cov.: 34 AF XY: 0.000594 AC XY: 429AN XY: 722226
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GnomAD4 genome ? AF: 0.00713 AC: 1084AN: 152112Hom.: 20 Cov.: 32 AF XY: 0.00725 AC XY: 539AN XY: 74350
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ExAC
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247
Asia WGS
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4
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3478
ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | May 20, 2018 | - - |
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
Benign
N
LIST_S2
Benign
T;T;.;T;T;T;T
MetaRNN
Benign
T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N;N;N;N;N
REVEL
Benign
Sift
Benign
T;T;T;T;D;T;T
Sift4G
Benign
T;T;T;T;T;T;T
Polyphen
0.0
.;.;B;.;.;B;.
Vest4
0.032, 0.036
MVP
MPC
0.15
ClinPred
T
GERP RS
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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