10-68572757-GT-CA

Variant names:

• chr10-68572757-GT-CA
• NM_030625.3:c.419_420delGTinsCA
• TET1 p.Cys140Ser

Variant summary

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

The NM_030625.3(TET1):​c.419_420delGTinsCA​(p.Cys140Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. 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. C140R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TET1 NM_030625.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.86
• Publications: 0 publications found

Genes affected

TET1 (HGNC:29484): (tet methylcytosine dioxygenase 1) DNA methylation is an epigenetic mechanism that is important for controlling gene expression. The protein encoded by this gene is a demethylase that belongs to the TET (ten-eleven translocation) family. Members of the TET protein family play a role in the DNA methylation process and gene activation. [provided by RefSeq, Sep 2015]

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030625.3. 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
	TET1	NM_030625.3	MANE Select	c.419_420delGTinsCA	p.Cys140Ser	missense	N/A	NP_085128.2	Q8NFU7-1
	TET1	NM_001406365.1		c.419_420delGTinsCA	p.Cys140Ser	missense	N/A	NP_001393294.1
	TET1	NM_001406373.1		c.419_420delGTinsCA	p.Cys140Ser	missense	N/A	NP_001393302.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TET1	ENST00000373644.5	TSL:1 MANE Select	c.419_420delGTinsCA	p.Cys140Ser	missense	N/A	ENSP00000362748.4	Q8NFU7-1
	TET1	ENST00000929765.1		c.419_420delGTinsCA	p.Cys140Ser	missense	N/A	ENSP00000599824.1
	TET1	ENST00000929763.1		c.419_420delGTinsCA	p.Cys140Ser	missense	N/A	ENSP00000599822.1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.9

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr10-70332514;