2-74046256-T-TC

Position:

• chr2-74046256-T-TC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001287491.2(TET3):​c.361-17dupC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 1,474,670 control chromosomes in the GnomAD database, including 63,881 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.31 (7883 hom., cov: 0)
  • Exomes 𝑓: 0.29 (55998 hom.)
• Consequence: TET3 NM_001287491.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0330

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 2-74046256-T-TC is Benign according to our data. Variant chr2-74046256-T-TC is described in ClinVar as [Benign]. Clinvar id is 1342287.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.413 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TET3	NM_001287491.2	c.361-17dupC		intron_variant		ENST00000409262.8	NP_001274420.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TET3	ENST00000409262.8	c.361-17dupC		intron_variant		1	NM_001287491.2	ENSP00000386869.3
TET3	ENST00000305799.8	c.82-17dupC		intron_variant		5		ENSP00000307803.8

Frequencies

GnomAD3 genomes AF: 0.311 AC: 47210 AN: 151884 Hom.: 7862 Cov.: 0

Gnomad AFR AF: 0.418

Gnomad AMI AF: 0.367

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.206

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.303

Gnomad OTH AF: 0.282

GnomAD3 exomes AF: 0.265 AC: 42267 AN: 159248 Hom.: 6224 AF XY: 0.265 AC XY: 22754 AN XY: 85778

Gnomad AFR exome AF: 0.418

Gnomad AMR exome AF: 0.185

Gnomad ASJ exome AF: 0.251

Gnomad EAS exome AF: 0.109

Gnomad SAS exome AF: 0.182

Gnomad FIN exome AF: 0.213

Gnomad NFE exome AF: 0.311

Gnomad OTH exome AF: 0.260

GnomAD4 exome AF: 0.287 AC: 379110 AN: 1322668 Hom.: 55998 Cov.: 32 AF XY: 0.285 AC XY: 183230 AN XY: 643858

Gnomad4 AFR exome AF: 0.421

Gnomad4 AMR exome AF: 0.199

Gnomad4 ASJ exome AF: 0.248

Gnomad4 EAS exome AF: 0.110

Gnomad4 SAS exome AF: 0.181

Gnomad4 FIN exome AF: 0.221

Gnomad4 NFE exome AF: 0.302

Gnomad4 OTH exome AF: 0.273

GnomAD4 genome AF: 0.311 AC: 47277 AN: 152002 Hom.: 7883 Cov.: 0 AF XY: 0.300 AC XY: 22294 AN XY: 74278

Gnomad4 AFR AF: 0.419

Gnomad4 AMR AF: 0.247

Gnomad4 ASJ AF: 0.254

Gnomad4 EAS AF: 0.111

Gnomad4 SAS AF: 0.190

Gnomad4 FIN AF: 0.206

Gnomad4 NFE AF: 0.303

Gnomad4 OTH AF: 0.279

Alfa AF: 0.286 Hom.: 657

Asia WGS AF: 0.156 AC: 546 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Beck-Fahrner syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs11426743; hg19: chr2-74273383;