rs3998860

Variant names:

• chr10-68646098-A-G
• rs3998860
• NM_030625.3:c.3369A>G

Your query was ambiguous. Multiple possible variants found:

• chr10-68646098-A-G
• chr10-68646098-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_030625.3(TET1):​c.3369A>G​(p.Ile1123Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.801 in 1,613,732 control chromosomes in the GnomAD database, including 523,176 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.72 (41118 hom., cov: 31)
  • Exomes 𝑓: 0.81 (482058 hom.)
• Consequence: TET1 NM_030625.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.405
• Publications: 48 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.0815608E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.817 is higher than 0.05.

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.3369A>G	p.Ile1123Met	missense	Exon 4 of 12	NP_085128.2	Q8NFU7-1
	TET1	NM_001406365.1		c.3369A>G	p.Ile1123Met	missense	Exon 4 of 13	NP_001393294.1
	TET1	NM_001406367.1		c.1458A>G	p.Ile486Met	missense	Exon 3 of 12	NP_001393296.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TET1	ENST00000373644.5	TSL:1 MANE Select	c.3369A>G	p.Ile1123Met	missense	Exon 4 of 12	ENSP00000362748.4	Q8NFU7-1
	TET1	ENST00000929765.1		c.3369A>G	p.Ile1123Met	missense	Exon 4 of 14	ENSP00000599824.1
	TET1	ENST00000929763.1		c.3369A>G	p.Ile1123Met	missense	Exon 4 of 13	ENSP00000599822.1

Frequencies

GnomAD3 genomes AF: 0.721 AC: 109582 AN: 151890 Hom.: 41116 Cov.: 31

Gnomad AFR AF: 0.493

Gnomad AMI AF: 0.911

Gnomad AMR AF: 0.754

Gnomad ASJ AF: 0.896

Gnomad EAS AF: 0.838

Gnomad SAS AF: 0.726

Gnomad FIN AF: 0.797

Gnomad MID AF: 0.835

Gnomad NFE AF: 0.819

Gnomad OTH AF: 0.761

GnomAD2 exomes AF: 0.777 AC: 194962 AN: 250830 AF XY: 0.783

Gnomad AFR exome AF: 0.485

Gnomad AMR exome AF: 0.724

Gnomad ASJ exome AF: 0.891

Gnomad EAS exome AF: 0.840

Gnomad FIN exome AF: 0.801

Gnomad NFE exome AF: 0.820

Gnomad OTH exome AF: 0.808

GnomAD4 exome AF: 0.810 AC: 1183593 AN: 1461724 Hom.: 482058 Cov.: 60 AF XY: 0.808 AC XY: 587858 AN XY: 727170

African (AFR) AF: 0.488 AC: 16344 AN: 33472

American (AMR) AF: 0.730 AC: 32638 AN: 44680

Ashkenazi Jewish (ASJ) AF: 0.890 AC: 23249 AN: 26134

East Asian (EAS) AF: 0.835 AC: 33157 AN: 39694

South Asian (SAS) AF: 0.740 AC: 63813 AN: 86246

European-Finnish (FIN) AF: 0.798 AC: 42587 AN: 53392

Middle Eastern (MID) AF: 0.857 AC: 4946 AN: 5768

European-Non Finnish (NFE) AF: 0.826 AC: 918033 AN: 1111952

Other (OTH) AF: 0.809 AC: 48826 AN: 60386

GnomAD4 genome AF: 0.721 AC: 109626 AN: 152008 Hom.: 41118 Cov.: 31 AF XY: 0.722 AC XY: 53644 AN XY: 74294

African (AFR) AF: 0.493 AC: 20404 AN: 41406

American (AMR) AF: 0.754 AC: 11510 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.896 AC: 3109 AN: 3468

East Asian (EAS) AF: 0.837 AC: 4328 AN: 5168

South Asian (SAS) AF: 0.728 AC: 3502 AN: 4812

European-Finnish (FIN) AF: 0.797 AC: 8435 AN: 10578

Middle Eastern (MID) AF: 0.816 AC: 240 AN: 294

European-Non Finnish (NFE) AF: 0.819 AC: 55665 AN: 67990

Other (OTH) AF: 0.759 AC: 1604 AN: 2112

Alfa AF: 0.795 Hom.: 201116

Bravo AF: 0.711

TwinsUK AF: 0.837 AC: 3103

ALSPAC AF: 0.818 AC: 3153

ESP6500AA AF: 0.499 AC: 2200

ESP6500EA AF: 0.835 AC: 7180

ExAC AF: 0.773 AC: 93837

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.80	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	12
DANN	Benign	0.88
DEOGEN2	Benign	0.027	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.081	N
LIST_S2	Benign	0.45	T
MetaRNN	Benign	0.0000011	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.41
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.15	N
REVEL	Benign	0.060
Sift	Benign	0.16	T
Sift4G	Benign	0.073	T
Polyphen		0.070	B
Vest4		0.034
MPC		0.050
ClinPred		0.0036	T
GERP RS		-3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.073
gMVP		0.054
Mutation Taster		=99/1	polymorphism (auto)

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: rs3998860; hg19: chr10-70405855; COSMIC: COSV65385549;