rs782311451
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_138425.4(C12orf57):c.127G>T(p.Ala43Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000496 in 1,614,044 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000048 ( 0 hom. )
Consequence
C12orf57
NM_138425.4 missense
NM_138425.4 missense
Scores
1
8
9
Clinical Significance
Conservation
PhyloP100: 5.84
Genes affected
C12orf57 (HGNC:29521): (chromosome 12 open reading frame 57) This gene is ubiquitously expressed in human tissues. It is required for development of the human corpus callosum. Mutations in this gene are associated with Temtamy syndrome (TEMTYS). Multiple 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 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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
C12orf57 | NM_138425.4 | c.127G>T | p.Ala43Ser | missense_variant | 2/3 | ENST00000229281.6 | NP_612434.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
C12orf57 | ENST00000229281.6 | c.127G>T | p.Ala43Ser | missense_variant | 2/3 | 1 | NM_138425.4 | ENSP00000229281.5 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152262Hom.: 0 Cov.: 33
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GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461782Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4AN XY: 727190
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152262Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74394
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2016 | - - |
Temtamy syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Sep 01, 2022 | This variant has not been reported in the literature in individuals affected with C12orf57-related conditions. This variant is present in population databases (rs782311451, gnomAD 0.0009%). This sequence change replaces alanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 43 of the C12orf57 protein (p.Ala43Ser). ClinVar contains an entry for this variant (Variation ID: 581132). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T;T;T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
D
LIST_S2
Benign
.;T;D;T;T
M_CAP
Uncertain
D
MetaRNN
Uncertain
T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;.;.;N;.
PROVEAN
Benign
N;.;N;N;.
REVEL
Uncertain
Sift
Benign
T;.;T;T;.
Sift4G
Benign
T;T;T;T;T
Polyphen
P;.;D;P;.
Vest4
0.41, 0.45, 0.39, 0.37
MutPred
Gain of disorder (P = 0.0382);Gain of disorder (P = 0.0382);Gain of disorder (P = 0.0382);Gain of disorder (P = 0.0382);.;
MVP
MPC
0.20
ClinPred
D
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