Variant 2-74003213-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001287491.2(TET3):c.360+47G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00696 in 1,547,692 control chromosomes in the GnomAD database, including 50 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0046 ( 2 hom., cov: 31)

Exomes 𝑓: 0.0072 ( 48 hom. )

Consequence

TET3
NM_001287491.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.281

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]

TET3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 2-74003213-G-A is Benign according to our data. Variant chr2-74003213-G-A is described in ClinVar as [Benign]. Clinvar id is 1342286.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00459 (697/151998) while in subpopulation NFE AF= 0.00792 (538/67956). AF 95% confidence interval is 0.00736. There are 2 homozygotes in gnomad4. There are 309 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TET3	NM_001287491.2 linkuse as main transcript	c.360+47G>A		intron_variant		ENST00000409262.8	NP_001274420.1	O43151-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TET3	ENST00000409262.8 linkuse as main transcript	c.360+47G>A		intron_variant		1	NM_001287491.2	ENSP00000386869.3		O43151-1
TET3	ENST00000305799.8 linkuse as main transcript	c.81+47G>A		intron_variant		5		ENSP00000307803.8		A0A5H1ZRP3

Frequencies

GnomAD3 genomes

AF:

0.00459

AC:

697

AN:

151880

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00131

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00295

Gnomad ASJ

AF:

0.00404

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00333

Gnomad FIN

AF:

0.00161

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00792

Gnomad OTH

AF:

0.00532

GnomAD3 exomes

AF:

0.00486

AC:

705

AN:

145128

Hom.:

AF XY:

0.00487

AC XY:

381

AN XY:

78186

show subpopulations

Gnomad AFR exome

AF:

0.000890

Gnomad AMR exome

AF:

0.00402

Gnomad ASJ exome

AF:

0.00314

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00467

Gnomad FIN exome

AF:

0.00166

Gnomad NFE exome

AF:

0.00785

Gnomad OTH exome

AF:

0.00615

GnomAD4 exome

AF:

0.00722

AC:

10080

AN:

1395694

Hom.:

Cov.:

AF XY:

0.00715

AC XY:

4920

AN XY:

688344

show subpopulations

Gnomad4 AFR exome

AF:

0.000951

Gnomad4 AMR exome

AF:

0.00407

Gnomad4 ASJ exome

AF:

0.00354

Gnomad4 EAS exome

AF:

0.0000280

Gnomad4 SAS exome

AF:

0.00435

Gnomad4 FIN exome

AF:

0.00233

Gnomad4 NFE exome

AF:

0.00830

Gnomad4 OTH exome

AF:

0.00646

GnomAD4 genome

AF:

0.00459

AC:

697

AN:

151998

Hom.:

Cov.:

AF XY:

0.00416

AC XY:

309

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.00130

Gnomad4 AMR

AF:

0.00295

Gnomad4 ASJ

AF:

0.00404

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00333

Gnomad4 FIN

AF:

0.00161

Gnomad4 NFE

AF:

0.00792

Gnomad4 OTH

AF:

0.00526

Alfa

AF:

0.00589

Hom.:

Bravo

AF:

0.00481

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Beck-Fahrner syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

DANN

Benign

0.94

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over