chr10-68684562-T-C

Variant names:

• chr10-68684562-T-C
• rs2030057
• NM_030625.3:c.5052+1589T>C

Variant summary

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

The NM_030625.3(TET1):​c.5052+1589T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.791 in 151,924 control chromosomes in the GnomAD database, including 47,785 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.79 (47785 hom., cov: 29)
• Consequence: TET1 NM_030625.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.287
• Publications: 4 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 (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.822 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TET1	NM_030625.3	c.5052+1589T>C		intron_variant	Intron 10 of 11	ENST00000373644.5	NP_085128.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TET1	ENST00000373644.5	c.5052+1589T>C		intron_variant	Intron 10 of 11	1	NM_030625.3	ENSP00000362748.4

Frequencies

GnomAD3 genomes AF: 0.791 AC: 120100 AN: 151806 Hom.: 47771 Cov.: 29

Gnomad AFR AF: 0.715

Gnomad AMI AF: 0.909

Gnomad AMR AF: 0.780

Gnomad ASJ AF: 0.887

Gnomad EAS AF: 0.841

Gnomad SAS AF: 0.770

Gnomad FIN AF: 0.806

Gnomad MID AF: 0.848

Gnomad NFE AF: 0.828

Gnomad OTH AF: 0.808

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

GnomAD4 genome AF: 0.791 AC: 120162 AN: 151924 Hom.: 47785 Cov.: 29 AF XY: 0.788 AC XY: 58546 AN XY: 74274

African (AFR) AF: 0.715 AC: 29588 AN: 41376

American (AMR) AF: 0.779 AC: 11881 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.887 AC: 3078 AN: 3470

East Asian (EAS) AF: 0.841 AC: 4333 AN: 5154

South Asian (SAS) AF: 0.771 AC: 3721 AN: 4826

European-Finnish (FIN) AF: 0.806 AC: 8517 AN: 10562

Middle Eastern (MID) AF: 0.830 AC: 244 AN: 294

European-Non Finnish (NFE) AF: 0.828 AC: 56275 AN: 67982

Other (OTH) AF: 0.807 AC: 1700 AN: 2106

Alfa AF: 0.807 Hom.: 16488

Bravo AF: 0.787

Asia WGS AF: 0.758 AC: 2635 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.9
DANN	Benign	0.48
PhyloP100		0.29
Mutation Taster		=100/0	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: rs2030057; hg19: chr10-70444319;