rs1684031108

Variant names:

• chr2-73986470-C-G
• rs1684031108
• NM_001287491.2:c.67C>G

Your query was ambiguous. Multiple possible variants found:

• chr2-73986470-C-G
• chr2-73986470-C-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.67C>G​(p.Arg23Gly) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R23C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TET3 NM_001287491.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.51
• 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=0.12584874).

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.67C>G	p.Arg23Gly	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.67C>G	p.Arg23Gly	missense	Exon 2 of 12	ENSP00000386869.3	O43151-1
	DGUOK-AS1	ENST00000804871.1		n.142G>C		non_coding_transcript_exon	Exon 1 of 2
	DGUOK-AS1	ENST00000804891.1		n.191G>C		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.040
BayesDel_addAF	Benign	-0.074	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	18
DANN	Benign	0.71
FATHMM_MKL	Benign	0.033	N
LIST_S2	Benign	0.28	T
MetaRNN	Benign	0.13	T
PhyloP100		3.5
Sift4G	Benign	0.47	T
Vest4		0.24
MVP		0.13
GERP RS		4.9
gMVP		0.23

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: rs1684031108; hg19: chr2-74213597;