Variant 10-96319378-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_004088.4(DNTT):c.495C>T(p.Asn165Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000366 in 1,613,680 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0020 ( 2 hom., cov: 33)

Exomes 𝑓: 0.00020 ( 1 hom. )

Consequence

DNTT
NM_004088.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.73

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 Likely_benign. Variant got -6 ACMG points.

BP6

Variant 10-96319378-C-T is Benign according to our data. Variant chr10-96319378-C-T is described in ClinVar as [Benign]. Clinvar id is 709704.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNTT	NM_004088.4 linkuse as main transcript	c.495C>T	p.Asn165Asn	synonymous_variant	3/11	ENST00000371174.5	NP_004079.3	P04053-1
DNTT	NM_001017520.2 linkuse as main transcript	c.495C>T	p.Asn165Asn	synonymous_variant	3/11		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.495C>T	p.Asn165Asn	synonymous_variant	3/11	1	NM_004088.4	ENSP00000360216.2		P04053-1
DNTT	ENST00000630152.1 linkuse as main transcript	c.495C>T	p.Asn165Asn	synonymous_variant	3/11	1		ENSP00000486733.1		P04053-2

Frequencies

GnomAD3 genomes

AF:

0.00198

AC:

301

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00707

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

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:

0.000478

GnomAD3 exomes

AF:

0.000398

AC:

100

AN:

251042

Hom.:

AF XY:

0.000265

AC XY:

AN XY:

135648

show subpopulations

Gnomad AFR exome

AF:

0.00597

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000882

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000198

AC:

289

AN:

1461414

Hom.:

Cov.:

AF XY:

0.000155

AC XY:

113

AN XY:

727008

show subpopulations

Gnomad4 AFR exome

AF:

0.00742

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.000563

GnomAD4 genome

AF:

0.00198

AC:

301

AN:

152266

Hom.:

Cov.:

AF XY:

0.00191

AC XY:

142

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.00705

Gnomad4 AMR

AF:

0.000458

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:

0.000473

Alfa

AF:

0.00116

Hom.:

Bravo

AF:

0.00230

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

8.9

DANN

Benign

0.62

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.22

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.22

Position offset: 12

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