Variant chr10-96324353-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_004088.4(DNTT):c.838G>C(p.Asp280His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00507 in 1,613,844 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0042 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0052 ( 24 hom. )

Consequence

DNTT
NM_004088.4 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.85

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010669142).

BP6

Variant 10-96324353-G-C is Benign according to our data. Variant chr10-96324353-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 791541.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNTT	NM_004088.4 linkuse as main transcript	c.838G>C	p.Asp280His	missense_variant	6/11	ENST00000371174.5	NP_004079.3	P04053-1
DNTT	NM_001017520.2 linkuse as main transcript	c.838G>C	p.Asp280His	missense_variant	6/11		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.838G>C	p.Asp280His	missense_variant	6/11	1	NM_004088.4	ENSP00000360216.2		P04053-1
DNTT	ENST00000630152.1 linkuse as main transcript	c.838G>C	p.Asp280His	missense_variant	6/11	1		ENSP00000486733.1		P04053-2

Frequencies

GnomAD3 genomes

AF:

0.00418

AC:

636

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00109

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00668

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00179

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00647

Gnomad OTH

AF:

0.00813

GnomAD3 exomes

AF:

0.00437

AC:

1098

AN:

251216

Hom.:

AF XY:

0.00432

AC XY:

586

AN XY:

135772

show subpopulations

Gnomad AFR exome

AF:

0.000923

Gnomad AMR exome

AF:

0.00399

Gnomad ASJ exome

AF:

0.00109

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00278

Gnomad FIN exome

AF:

0.00351

Gnomad NFE exome

AF:

0.00646

Gnomad OTH exome

AF:

0.00653

GnomAD4 exome

AF:

0.00516

AC:

7542

AN:

1461580

Hom.:

Cov.:

AF XY:

0.00509

AC XY:

3704

AN XY:

727098

show subpopulations

Gnomad4 AFR exome

AF:

0.00117

Gnomad4 AMR exome

AF:

0.00481

Gnomad4 ASJ exome

AF:

0.00180

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00267

Gnomad4 FIN exome

AF:

0.00382

Gnomad4 NFE exome

AF:

0.00581

Gnomad4 OTH exome

AF:

0.00472

GnomAD4 genome

AF:

0.00418

AC:

636

AN:

152264

Hom.:

Cov.:

AF XY:

0.00396

AC XY:

295

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.00108

Gnomad4 AMR

AF:

0.00667

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00179

Gnomad4 NFE

AF:

0.00647

Gnomad4 OTH

AF:

0.00805

Alfa

AF:

0.00560

Hom.:

Bravo

AF:

0.00488

TwinsUK

AF:

0.00647

AC:

ALSPAC

AF:

0.00493

AC:

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00512

AC:

ExAC

AF:

0.00422

AC:

513

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00867

EpiControl

AF:

0.00824

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.21

T;.

Eigen

Benign

0.14

Eigen_PC

Benign

0.053

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.76

T;T

MetaRNN

Benign

0.011

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

L;L

PrimateAI

Benign

0.42

PROVEAN

Benign

-2.0

N;.

REVEL

Benign

0.11

Sift

Uncertain

0.013

D;.

Sift4G

Benign

0.10

T;T

Polyphen

0.99

D;D

Vest4

0.42

MVP

0.76

MPC

0.13

ClinPred

0.028

GERP RS

3.8

Varity_R

0.12

gMVP

0.50

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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