NM_001287491.2:c.360+15484T>C

Variant names:

• chr2-74018650-T-C
• rs6546886
• NM_001287491.2:c.360+15484T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001287491.2(TET3):​c.360+15484T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 152,084 control chromosomes in the GnomAD database, including 14,868 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.39 (14868 hom., cov: 31)
• Consequence: TET3 NM_001287491.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.10
• Publications: 16 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.7 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.360+15484T>C		intron	N/A	NP_001274420.1	O43151-1
	TET3	NM_001366022.1		c.81+15484T>C		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.360+15484T>C		intron	N/A	ENSP00000386869.3	O43151-1
	TET3	ENST00000305799.9	TSL:5	c.81+15484T>C		intron	N/A	ENSP00000307803.8	A0A5H1ZRP3
	TET3	ENST00000718303.1		c.-81+15484T>C		intron	N/A	ENSP00000520736.1	A0ABB0MVC9

Frequencies

GnomAD3 genomes AF: 0.393 AC: 59723 AN: 151964 Hom.: 14819 Cov.: 31

Gnomad AFR AF: 0.707

Gnomad AMI AF: 0.365

Gnomad AMR AF: 0.278

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.188

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.261

Gnomad NFE AF: 0.304

Gnomad OTH AF: 0.339

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.393 AC: 59823 AN: 152084 Hom.: 14868 Cov.: 31 AF XY: 0.381 AC XY: 28310 AN XY: 74380

African (AFR) AF: 0.707 AC: 29302 AN: 41432

American (AMR) AF: 0.278 AC: 4251 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 819 AN: 3472

East Asian (EAS) AF: 0.112 AC: 580 AN: 5186

South Asian (SAS) AF: 0.188 AC: 908 AN: 4830

European-Finnish (FIN) AF: 0.204 AC: 2165 AN: 10590

Middle Eastern (MID) AF: 0.260 AC: 76 AN: 292

European-Non Finnish (NFE) AF: 0.304 AC: 20682 AN: 67974

Other (OTH) AF: 0.335 AC: 709 AN: 2114

Alfa AF: 0.328 Hom.: 34139

Bravo AF: 0.416

Asia WGS AF: 0.177 AC: 619 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	8.2
DANN	Benign	0.79
PhyloP100		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

Other links and lift over

dbSNP: rs6546886; hg19: chr2-74245777;