16-30429959-T-A

Position:

chr16-30429959-T-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_024096.2(DCTPP1):c.22A>T(p.Ile8Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000197 in 1,576,402 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

DCTPP1
NM_024096.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.27

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04626614).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCTPP1	NM_024096.2 link	c.22A>T	p.Ile8Phe	missense_variant	1/3	ENST00000319285.5	NP_077001.1	Q9H773
DCTPP1	NR_134470.2 link	n.72A>T		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DCTPP1	ENST00000319285.5 link	c.22A>T	p.Ile8Phe	missense_variant	1/3	1	NM_024096.2	ENSP00000322524.4	Q9H773
ZNF771	ENST00000566625.2 link	c.*1062T>A		3_prime_UTR_variant	3/3	1		ENSP00000460549.1	I3L3L5
DCTPP1	ENST00000567983.1 link	c.22A>T	p.Ile8Phe	missense_variant	1/2	5		ENSP00000456612.1	H3BSA6
DCTPP1	ENST00000565758.1 link	c.-367A>T		5_prime_UTR_variant	1/3	3		ENSP00000460933.1	H3BPN2

Frequencies

GnomAD3 genomes

AF:

0.0000791

AC:

AN:

151758

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000657

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:

0.000959

GnomAD3 exomes

AF:

0.00000960

AC:

AN:

208244

Hom.:

AF XY:

0.00000871

AC XY:

AN XY:

114820

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000354

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:

0.0000105

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000133

AC:

AN:

1424644

Hom.:

Cov.:

AF XY:

0.00000988

AC XY:

AN XY:

708180

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000175

Gnomad4 ASJ exome

AF:

0.0000800

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000639

Gnomad4 OTH exome

AF:

0.0000511

GnomAD4 genome

AF:

0.0000791

AC:

AN:

151758

Hom.:

Cov.:

AF XY:

0.0000405

AC XY:

AN XY:

74096

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000657

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:

0.000959

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.000136

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

Jun 18, 2021

The c.22A>T (p.I8F) alteration is located in exon 1 (coding exon 1) of the DCTPP1 gene. This alteration results from a A to T substitution at nucleotide position 22, causing the isoleucine (I) at amino acid position 8 to be replaced by a phenylalanine (F). 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

0.088

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.59

CADD

Benign

0.17

DANN

Benign

0.58

DEOGEN2

Benign

0.028

T;T

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.051

LIST_S2

Benign

0.26

T;T

M_CAP

Benign

0.00090

MetaRNN

Benign

0.046

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;.

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.52

N;N

REVEL

Benign

0.030

Sift

Benign

0.061

T;D

Sift4G

Benign

0.19

T;.

Polyphen

0.0010

B;.

Vest4

0.21

MutPred

0.16

Gain of methylation at R9 (P = 0.0449);Gain of methylation at R9 (P = 0.0449);

MVP

0.16

MPC

0.29

ClinPred

0.091

GERP RS

-8.2

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.0

Varity_R

0.061

gMVP

0.41

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