chr2-73986475-G-T

Variant names:

• chr2-73986475-G-T
• NM_001287491.2:c.72G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001287491.2(TET3):​c.72G>T​(p.Gln24His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 8/10 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TET3 NM_001287491.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.992
• Publications: 0 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]

DGUOK-AS1 (HGNC:43441): (DGUOK antisense RNA 1)

ENSG00000235499 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1366112).

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.72G>T	p.Gln24His	missense	Exon 2 of 12	NP_001274420.1	O43151-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TET3	ENST00000409262.8	TSL:1 MANE Select	c.72G>T	p.Gln24His	missense	Exon 2 of 12	ENSP00000386869.3	O43151-1
	DGUOK-AS1	ENST00000804871.1		n.137C>A		non_coding_transcript_exon	Exon 1 of 2
	DGUOK-AS1	ENST00000804891.1		n.186C>A		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.061	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	21
DANN	Benign	0.89
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.69	T
MetaRNN	Benign	0.14	T
PhyloP100		0.99
Sift4G	Pathogenic	0.0	D
Vest4		0.20
MVP		0.17
GERP RS		2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.2
gMVP		0.33

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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

hg19: chr2-74213602;