2-74046356-C-A

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM2BP4_ModerateBP6_ModerateBP7BS1

The NM_001287491.2(TET3):​c.439C>A​(p.Arg147Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000667 in 1,529,192 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00017 ( 1 hom., cov: 32)
Exomes 𝑓: 0.000055 ( 0 hom. )

Consequence

TET3
NM_001287491.2 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.460
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.39).
BP6
Variant 2-74046356-C-A is Benign according to our data. Variant chr2-74046356-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 2651034.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.46 with no splicing effect.
BS1
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000171 (26/152334) while in subpopulation AMR AF= 0.00131 (20/15302). AF 95% confidence interval is 0.000865. There are 1 homozygotes in gnomad4. There are 15 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TET3NM_001287491.2 linkc.439C>A p.Arg147Arg synonymous_variant Exon 4 of 12 ENST00000409262.8 NP_001274420.1 O43151-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TET3ENST00000409262.8 linkc.439C>A p.Arg147Arg synonymous_variant Exon 4 of 12 1 NM_001287491.2 ENSP00000386869.3 O43151-1
TET3ENST00000305799.8 linkc.160C>A p.Arg54Arg synonymous_variant Exon 3 of 11 5 ENSP00000307803.8 A0A5H1ZRP3

Frequencies

GnomAD3 genomes
AF:
0.000171
AC:
26
AN:
152216
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000724
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000854
AC:
15
AN:
175620
Hom.:
0
AF XY:
0.000118
AC XY:
11
AN XY:
93108
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000278
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000709
Gnomad OTH exome
AF:
0.000746
GnomAD4 exome
AF:
0.0000552
AC:
76
AN:
1376858
Hom.:
0
Cov.:
33
AF XY:
0.0000502
AC XY:
34
AN XY:
676748
show subpopulations
Gnomad4 AFR exome
AF:
0.0000328
Gnomad4 AMR exome
AF:
0.000266
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000255
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000512
Gnomad4 OTH exome
AF:
0.000194
GnomAD4 genome
AF:
0.000171
AC:
26
AN:
152334
Hom.:
1
Cov.:
32
AF XY:
0.000201
AC XY:
15
AN XY:
74492
show subpopulations
Gnomad4 AFR
AF:
0.0000721
Gnomad4 AMR
AF:
0.00131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.000189

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Apr 01, 2023
CeGaT Center for Human Genetics Tuebingen
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

TET3: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.39
CADD
Benign
5.2
DANN
Benign
0.60

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs182958671; hg19: chr2-74273483; API