Variant chr10-96318387-C-T 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.239C>T(p.Ser80Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000958 in 1,461,090 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

DNTT
NM_004088.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.20

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.239C>T	p.Ser80Leu	missense_variant	2/11	ENST00000371174.5	NP_004079.3	P04053-1
DNTT	NM_001017520.2 linkuse as main transcript	c.239C>T	p.Ser80Leu	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.239C>T	p.Ser80Leu	missense_variant	2/11	1	NM_004088.4	ENSP00000360216.2		P04053-1
DNTT	ENST00000630152.1 linkuse as main transcript	c.239C>T	p.Ser80Leu	missense_variant	2/11	1		ENSP00000486733.1		P04053-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000958

AC:

AN:

1461090

Hom.:

Cov.:

AF XY:

0.00000826

AC XY:

AN XY:

726790

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000108

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000151

EpiCase

AF:

0.0000546

EpiControl

AF:

0.00

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

Jan 31, 2024

The c.239C>T (p.S80L) alteration is located in exon 2 (coding exon 2) of the DNTT gene. This alteration results from a C to T substitution at nucleotide position 239, causing the serine (S) at amino acid position 80 to be replaced by a leucine (L). 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

0.11

BayesDel_addAF

Benign

-0.021

BayesDel_noAF

Benign

-0.27

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.45

T;.

Eigen

Pathogenic

0.76

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.91

D;D

M_CAP

Benign

0.072

MetaRNN

Uncertain

0.72

D;D

MetaSVM

Benign

-0.38

MutationAssessor

Pathogenic

2.9

M;M

PrimateAI

Uncertain

0.60

PROVEAN

Pathogenic

-4.6

D;.

REVEL

Uncertain

0.31

Sift

Uncertain

0.0020

D;.

Sift4G

Uncertain

0.0050

D;D

Polyphen

1.0

D;D

Vest4

0.53

MutPred

0.67

Loss of disorder (P = 0.012);Loss of disorder (P = 0.012);

MVP

0.79

MPC

0.46

ClinPred

1.0

GERP RS

5.6

Varity_R

0.49

gMVP

0.64

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