NM_030625.3:c.-123+2615G>A

Variant names:

• chr10-68563357-G-A
• rs10762231
• NM_030625.3:c.-123+2615G>A

Variant summary

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

The NM_030625.3(TET1):​c.-123+2615G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.424 in 152,132 control chromosomes in the GnomAD database, including 14,149 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 0.42 (14149 hom., cov: 33)
• Consequence: TET1 NM_030625.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.210
• Publications: 6 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=-0.73).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.513 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TET1	NM_030625.3	MANE Select	c.-123+2615G>A		intron	N/A	NP_085128.2
	TET1	NM_001406365.1		c.-123+2615G>A		intron	N/A	NP_001393294.1
	TET1	NM_001406373.1		c.-123+2615G>A		intron	N/A	NP_001393302.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TET1	ENST00000373644.5	TSL:1 MANE Select	c.-123+2615G>A		intron	N/A	ENSP00000362748.4

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64401 AN: 152016 Hom.: 14134 Cov.: 33

Gnomad AFR AF: 0.520

Gnomad AMI AF: 0.400

Gnomad AMR AF: 0.409

Gnomad ASJ AF: 0.270

Gnomad EAS AF: 0.429

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.481

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.375

Gnomad OTH AF: 0.374

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

GnomAD4 genome AF: 0.424 AC: 64461 AN: 152132 Hom.: 14149 Cov.: 33 AF XY: 0.426 AC XY: 31711 AN XY: 74384

African (AFR) AF: 0.519 AC: 21542 AN: 41486

American (AMR) AF: 0.410 AC: 6262 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.270 AC: 936 AN: 3466

East Asian (EAS) AF: 0.429 AC: 2220 AN: 5178

South Asian (SAS) AF: 0.346 AC: 1669 AN: 4828

European-Finnish (FIN) AF: 0.481 AC: 5093 AN: 10584

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.375 AC: 25483 AN: 67990

Other (OTH) AF: 0.375 AC: 792 AN: 2114

Alfa AF: 0.384 Hom.: 10653

Bravo AF: 0.426

Asia WGS AF: 0.370 AC: 1290 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	7.9
DANN	Benign	0.51
PhyloP100		0.21
Mutation Taster		=98/2	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: rs10762231; hg19: chr10-70323114;