10-68572598-C-G

Variant names:

• chr10-68572598-C-G
• rs140677396
• NM_030625.3:c.260C>G

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_030625.3(TET1):​c.260C>G​(p.Thr87Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00124 in 1,614,172 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0013 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (4 hom.)
• Consequence: TET1 NM_030625.3 missense
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.432
• Publications: 5 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0063821375).
• BP6: Variant 10-68572598-C-G is Benign according to our data. Variant chr10-68572598-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3043946.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Homozygotes in GnomAd4 at 2 gene

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.260C>G	p.Thr87Ser	missense	Exon 2 of 12	NP_085128.2	Q8NFU7-1
	TET1	NM_001406365.1		c.260C>G	p.Thr87Ser	missense	Exon 2 of 13	NP_001393294.1
	TET1	NM_001406373.1		c.260C>G	p.Thr87Ser	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.260C>G	p.Thr87Ser	missense	Exon 2 of 12	ENSP00000362748.4	Q8NFU7-1
	TET1	ENST00000929765.1		c.260C>G	p.Thr87Ser	missense	Exon 2 of 14	ENSP00000599824.1
	TET1	ENST00000929763.1		c.260C>G	p.Thr87Ser	missense	Exon 2 of 13	ENSP00000599822.1

Frequencies

GnomAD3 genomes AF: 0.00131 AC: 199 AN: 152162 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00179

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00251

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.00126 AC: 316 AN: 251456 AF XY: 0.00124

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00180

Gnomad NFE exome AF: 0.00234

Gnomad OTH exome AF: 0.000978

GnomAD4 exome AF: 0.00123 AC: 1798 AN: 1461892 Hom.: 4 Cov.: 33 AF XY: 0.00130 AC XY: 946 AN XY: 727248

African (AFR) AF: 0.000299 AC: 10 AN: 33480

American (AMR) AF: 0.0000894 AC: 4 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000230 AC: 6 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00228 AC: 122 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00146 AC: 1618 AN: 1112010

Other (OTH) AF: 0.000629 AC: 38 AN: 60396

GnomAD4 genome AF: 0.00131 AC: 199 AN: 152280 Hom.: 2 Cov.: 32 AF XY: 0.00130 AC XY: 97 AN XY: 74436

African (AFR) AF: 0.0000722 AC: 3 AN: 41578

American (AMR) AF: 0.000131 AC: 2 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.000577 AC: 2 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00179 AC: 19 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00251 AC: 171 AN: 68024

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.00195 Hom.: 1

Bravo AF: 0.000903

TwinsUK AF: 0.00135 AC: 5

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00151 AC: 13

ExAC AF: 0.00139 AC: 169

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00147

EpiControl AF: 0.00124

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	TET1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	12
DANN	Uncertain	0.98
DEOGEN2	Benign	0.10	T
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.0085	T
MetaRNN	Benign	0.0064	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.81	L
PhyloP100		0.43
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.011
Sift	Uncertain	0.010	D
Sift4G	Benign	0.11	T
Polyphen		0.12	B
Vest4		0.12
MutPred		0.13		Loss of sheet (P = 0.0181)
MVP		0.043
MPC		0.064
ClinPred		0.015	T
GERP RS		3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.090
gMVP		0.053
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs140677396; hg19: chr10-70332355;