2-73986475-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate

The NM_001287491.2(TET3):​c.72G>T​(p.Gln24His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 8/10 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

TET3
NM_001287491.2 missense

Scores

1
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.992
Variant links:
Genes affected
TET3 (HGNC:28313): (tet methylcytosine dioxygenase 3) Enables methyl-CpG binding activity and zinc ion binding activity. Involved in histone H3-K4 trimethylation; positive regulation of transcription by RNA polymerase II; and protein O-linked glycosylation. Predicted to be located in cytoplasm and male pronucleus. Predicted to be active in nucleus. Biomarker of esophagus squamous cell carcinoma. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), TET3. . Gene score misZ 2.878 (greater than the threshold 3.09). Trascript score misZ 3.5386 (greater than threshold 3.09). GenCC has associacion of gene with Beck-Fahrner syndrome.
BP4
Computational evidence support a benign effect (MetaRNN=0.1366112).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TET3NM_001287491.2 linkuse as main transcriptc.72G>T p.Gln24His missense_variant 2/12 ENST00000409262.8 NP_001274420.1 O43151-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TET3ENST00000409262.8 linkuse as main transcriptc.72G>T p.Gln24His missense_variant 2/121 NM_001287491.2 ENSP00000386869.3 O43151-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingGeneDxMay 09, 2024Has not been previously published as pathogenic or benign to our knowledge; No data available from control populations to assess the frequency of this variant; In silico analysis does not support a benign or deleterious effect of this variant on protein structure/function -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.19
BayesDel_addAF
Benign
-0.061
T
BayesDel_noAF
Benign
-0.32
CADD
Benign
21
DANN
Benign
0.89
FATHMM_MKL
Benign
0.60
D
LIST_S2
Benign
0.69
T
MetaRNN
Benign
0.14
T
Sift4G
Pathogenic
0.0
D
Vest4
0.20
MVP
0.17
GERP RS
2.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.2
gMVP
0.33

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.070
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-74213602; API