chr2-74046256-T-TC

Variant names:

• chr2-74046256-T-TC
• rs11426743
• NM_001287491.2:c.361-17dupC

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• Beck-Fahrner syndrome

  Inheritance: AD, AR, SD Classification: DEFINITIVE, STRONG, MODERATE, LIMITED Submitted by: PanelApp Australia, G2P, Illumina, ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001287491.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TET3	NM_001287491.2	MANE Select	c.361-17dupC		intron	N/A	NP_001274420.1	O43151-1
	TET3	NM_001366022.1		c.82-17dupC		intron	N/A	NP_001352951.1	A0A5H1ZRP3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TET3	ENST00000409262.8	TSL:1 MANE Select	c.361-22_361-21insC		intron	N/A	ENSP00000386869.3	O43151-1
	TET3	ENST00000305799.9	TSL:5	c.82-22_82-21insC		intron	N/A	ENSP00000307803.8	A0A5H1ZRP3
	TET3	ENST00000718303.1		c.-80-27293_-80-27292insC		intron	N/A	ENSP00000520736.1	A0ABB0MVC9

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

GnomAD2 exomes AF: 0.265 AC: 42267 AN: 159248 AF XY: 0.265

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 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

African (AFR) AF: 0.421 AC: 12472 AN: 29638

American (AMR) AF: 0.199 AC: 5004 AN: 25180

Ashkenazi Jewish (ASJ) AF: 0.248 AC: 4735 AN: 19072

East Asian (EAS) AF: 0.110 AC: 4153 AN: 37632

South Asian (SAS) AF: 0.181 AC: 10844 AN: 60054

European-Finnish (FIN) AF: 0.221 AC: 10597 AN: 47974

Middle Eastern (MID) AF: 0.234 AC: 1210 AN: 5170

European-Non Finnish (NFE) AF: 0.302 AC: 315251 AN: 1043668

Other (OTH) AF: 0.273 AC: 14844 AN: 54280

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

African (AFR) AF: 0.419 AC: 17344 AN: 41436

American (AMR) AF: 0.247 AC: 3775 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.254 AC: 883 AN: 3470

East Asian (EAS) AF: 0.111 AC: 573 AN: 5168

South Asian (SAS) AF: 0.190 AC: 914 AN: 4818

European-Finnish (FIN) AF: 0.206 AC: 2172 AN: 10566

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.303 AC: 20619 AN: 67946

Other (OTH) AF: 0.279 AC: 589 AN: 2114

Alfa AF: 0.286 Hom.: 657

Asia WGS AF: 0.156 AC: 546 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Beck-Fahrner syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.033
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11426743; hg19: chr2-74273383;