10-68572757-G-C

Variant names:

• chr10-68572757-G-C
• rs138665678
• NM_030625.3:c.419G>C

Variant summary

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

The NM_030625.3(TET1):​c.419G>C​(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. In-silico tool predicts a benign outcome for this variant. 15/22 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. 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: 1.56
• 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12271136).

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.419G>C	p.Cys140Ser	missense	Exon 2 of 12	NP_085128.2	Q8NFU7-1
	TET1	NM_001406365.1		c.419G>C	p.Cys140Ser	missense	Exon 2 of 13	NP_001393294.1
	TET1	NM_001406373.1		c.419G>C	p.Cys140Ser	missense	Exon 2 of 10	NP_001393302.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TET1	ENST00000373644.5	TSL:1 MANE Select	c.419G>C	p.Cys140Ser	missense	Exon 2 of 12	ENSP00000362748.4	Q8NFU7-1
	TET1	ENST00000929765.1		c.419G>C	p.Cys140Ser	missense	Exon 2 of 14	ENSP00000599824.1
	TET1	ENST00000929763.1		c.419G>C	p.Cys140Ser	missense	Exon 2 of 13	ENSP00000599822.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	14
DANN	Benign	0.78
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.6	L
PhyloP100		1.6
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.15
Sift	Uncertain	0.0060	D
Sift4G	Benign	0.40	T
Polyphen		0.079	B
Vest4		0.32
MutPred		0.47		Gain of disorder (P = 0.0076)
MVP		0.043
MPC		0.056
ClinPred		0.17	T
GERP RS		3.1
Varity_R		0.30
gMVP		0.071
Mutation Taster		=98/2	polymorphism

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: rs138665678; hg19: chr10-70332514;