Variant chr10-96318414-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004088.4(DNTT):c.266A>C(p.Gln89Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000682 in 1,613,692 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

DNTT
NM_004088.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.58

Variant links:

Genes affected

DNTT (HGNC:2983): (DNA nucleotidylexotransferase) This gene is a member of the DNA polymerase type-X family and encodes a template-independent DNA polymerase that catalyzes the addition of deoxynucleotides to the 3'-hydroxyl terminus of oligonucleotide primers. In vivo, the encoded protein is expressed in a restricted population of normal and malignant pre-B and pre-T lymphocytes during early differentiation, where it generates antigen receptor diversity by synthesizing non-germ line elements (N-regions) at the junctions of rearranged Ig heavy chain and T cell receptor gene segments. Alternatively spliced transcript variants encoding different isoforms of this gene have been described. [provided by RefSeq, Jul 2008]

DNTT links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNTT	NM_004088.4 linkuse as main transcript	c.266A>C	p.Gln89Pro	missense_variant	2/11	ENST00000371174.5	NP_004079.3	P04053-1
DNTT	NM_001017520.2 linkuse as main transcript	c.266A>C	p.Gln89Pro	missense_variant	2/11		NP_001017520.1	P04053-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNTT	ENST00000371174.5 linkuse as main transcript	c.266A>C	p.Gln89Pro	missense_variant	2/11	1	NM_004088.4	ENSP00000360216.2		P04053-1
DNTT	ENST00000630152.1 linkuse as main transcript	c.266A>C	p.Gln89Pro	missense_variant	2/11	1		ENSP00000486733.1		P04053-2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000684

AC:

AN:

1461494

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727032

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000810

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152198

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 01, 2024

The c.266A>C (p.Q89P) alteration is located in exon 2 (coding exon 2) of the DNTT gene. This alteration results from a A to C substitution at nucleotide position 266, causing the glutamine (Q) at amino acid position 89 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.052

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.41

T;.

Eigen

Uncertain

0.27

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Benign

0.55

LIST_S2

Benign

0.79

T;T

M_CAP

Benign

0.026

MetaRNN

Uncertain

0.52

D;D

MetaSVM

Benign

-0.58

MutationAssessor

Uncertain

2.4

M;M

PrimateAI

Benign

0.28

PROVEAN

Uncertain

-3.0

D;.

REVEL

Benign

0.22

Sift

Uncertain

0.012

D;.

Sift4G

Uncertain

0.019

D;D

Polyphen

0.69

P;P

Vest4

0.43

MutPred

0.58

Gain of methylation at K92 (P = 0.0862);Gain of methylation at K92 (P = 0.0862);

MVP

0.74

MPC

0.43

ClinPred

0.98

GERP RS

4.4

Varity_R

0.66

gMVP

0.80

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over