Variant chr20-45801127-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_052951.3(DNTTIP1):c.426G>C(p.Glu142Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,838 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

DNTTIP1
NM_052951.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0210

Variant links:

Genes affected

DNTTIP1 (HGNC:16160): (deoxynucleotidyltransferase terminal interacting protein 1) DNTTIP1 binds DNA and enhances the activity of terminal deoxynucleotidyltransferase (TDT, or DNTT; MIM 187410), a DNA polymerase that catalyzes the polymerization of DNA in the absence of a DNA template (Yamashita et al., 2001 [PubMed 11473582]).[supplied by OMIM, Mar 2008]

DNTTIP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11647886).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNTTIP1	NM_052951.3 linkuse as main transcript	c.426G>C	p.Glu142Asp	missense_variant	5/13	ENST00000372622.8	NP_443183.1	Q9H147
DNTTIP1	XM_024451823.2 linkuse as main transcript	c.306G>C	p.Glu102Asp	missense_variant	5/13		XP_024307591.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DNTTIP1	ENST00000372622.8 linkuse as main transcript	c.426G>C	p.Glu142Asp	missense_variant	5/13	1	NM_052951.3	ENSP00000361705.3	Q9H147
DNTTIP1	ENST00000456939.5 linkuse as main transcript	c.276G>C	p.Glu92Asp	missense_variant	4/12	5		ENSP00000401024.1	H7C1M5
DNTTIP1	ENST00000435014.1 linkuse as main transcript	c.204G>C	p.Glu68Asp	missense_variant	3/10	5		ENSP00000400573.1	H7C1J2
DNTTIP1	ENST00000415790.5 linkuse as main transcript	c.306G>C	p.Glu102Asp	missense_variant	4/6	3		ENSP00000392509.1	F2Z2A4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251474

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.00000410

AC:

AN:

1461838

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.0000662

GnomAD4 genome

Cov.:

Asia WGS

AF:

0.00115

AC:

AN:

3478

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

Oct 30, 2024

The c.426G>C (p.E142D) alteration is located in exon 5 (coding exon 5) of the DNTTIP1 gene. This alteration results from a G to C substitution at nucleotide position 426, causing the glutamic acid (E) at amino acid position 142 to be replaced by an aspartic acid (D). 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

0.090

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.0082

T;T

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.20

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.74

T;T

M_CAP

Benign

0.0038

MetaRNN

Benign

0.12

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.4

L;.

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-0.27

N;N

REVEL

Benign

0.054

Sift

Benign

0.54

T;T

Sift4G

Benign

0.46

T;T

Polyphen

0.025

B;.

Vest4

0.21

MutPred

0.23

Loss of disorder (P = 0.1872);.;

MVP

0.54

MPC

0.67

ClinPred

0.079

GERP RS

-0.79

Varity_R

0.13

gMVP

0.19

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