Variant 16-30424342-C-T 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_024096.2(DCTPP1):c.404G>A(p.Arg135His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000192 in 1,614,212 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000016 ( 1 hom. )

Consequence

DCTPP1
NM_024096.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.55

Variant links:

Genes affected

DCTPP1 (HGNC:28777): (dCTP pyrophosphatase 1) The protein encoded by this gene is dCTP pyrophosphatase, which converts dCTP to dCMP and inorganic pyrophosphate. The encoded protein also displays weak activity against dTTP and dATP, but none against dGTP. This protein may be responsible for eliminating excess dCTP after DNA synthesis and may prevent overmethylation of CpG islands. Three transcript variants, one protein-coding and the other two non-protein coding, have been found for this gene. [provided by RefSeq, Dec 2015]

DCTPP1 links:

ZNF771 (HGNC:29653): (zinc finger protein 771) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Located in nucleolus and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ZNF771 links:

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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=0.07535353).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCTPP1	NM_024096.2 link	c.404G>A	p.Arg135His	missense_variant	3/3	ENST00000319285.5	NP_077001.1	Q9H773
DCTPP1	NR_134470.2 link	n.479G>A		non_coding_transcript_exon_variant	3/3
DCTPP1	NR_134471.2 link	n.515G>A		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCTPP1	ENST00000319285.5 link	c.404G>A	p.Arg135His	missense_variant	3/3	1	NM_024096.2	ENSP00000322524.4		Q9H773

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000398

AC:

AN:

251384

Hom.:

AF XY:

0.0000442

AC XY:

AN XY:

135874

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000326

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000164

AC:

AN:

1461872

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000302

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000899

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000459

AC:

AN:

152340

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.0000721

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000473

Bravo

AF:

0.0000340

ExAC

AF:

0.0000576

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

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

Jul 13, 2021

The c.404G>A (p.R135H) alteration is located in exon 3 (coding exon 3) of the DCTPP1 gene. This alteration results from a G to A substitution at nucleotide position 404, causing the arginine (R) at amino acid position 135 to be replaced by a histidine (H). 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

0.13

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.042

T;T;.;.;.

Eigen

Benign

-0.17

Eigen_PC

Benign

-0.029

FATHMM_MKL

Uncertain

0.78

LIST_S2

Uncertain

0.90

D;T;.;.;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.075

T;T;T;T;T

MetaSVM

Benign

-0.89

MutationAssessor

Benign

1.7

L;.;.;.;.

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.74

N;N;.;.;.

REVEL

Benign

0.064

Sift

Benign

0.20

T;D;.;.;.

Sift4G

Benign

0.23

T;T;T;T;T

Polyphen

0.036

B;.;.;.;.

Vest4

0.067

MVP

0.55

MPC

0.24

ClinPred

0.072

GERP RS

5.5

Varity_R

0.033

gMVP

0.34

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