chr2-74018650-T-C

Position:

• chr2-74018650-T-C

Variant summary

Our verdict is Benign. Variant got -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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TET3	NM_001287491.2	c.360+15484T>C		intron_variant		ENST00000409262.8	NP_001274420.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TET3	ENST00000409262.8	c.360+15484T>C		intron_variant		1	NM_001287491.2	ENSP00000386869.3
TET3	ENST00000305799.8	c.81+15484T>C		intron_variant		5		ENSP00000307803.8

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

Gnomad4 AFR AF: 0.707

Gnomad4 AMR AF: 0.278

Gnomad4 ASJ AF: 0.236

Gnomad4 EAS AF: 0.112

Gnomad4 SAS AF: 0.188

Gnomad4 FIN AF: 0.204

Gnomad4 NFE AF: 0.304

Gnomad4 OTH AF: 0.335

Alfa AF: 0.312 Hom.: 14169

Bravo AF: 0.416

Asia WGS AF: 0.177 AC: 619 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

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: rs6546886; hg19: chr2-74245777;