16-30424435-A-G

Position:

• chr16-30424435-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_024096.2(DCTPP1):​c.311T>C​(p.Val104Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: DCTPP1 NM_024096.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.68

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]

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]

DCTPP1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCTPP1	NM_024096.2	c.311T>C	p.Val104Ala	missense_variant	3/3	ENST00000319285.5	NP_077001.1
DCTPP1	NR_134470.2	n.386T>C		non_coding_transcript_exon_variant	3/3
DCTPP1	NR_134471.2	n.422T>C		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCTPP1	ENST00000319285.5	c.311T>C	p.Val104Ala	missense_variant	3/3	1	NM_024096.2	ENSP00000322524.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 09, 2021

The c.311T>C (p.V104A) alteration is located in exon 3 (coding exon 3) of the DCTPP1 gene. This alteration results from a T to C substitution at nucleotide position 311, causing the valine (V) at amino acid position 104 to be replaced by an alanine (A). 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	Uncertain	0.44
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.0078	T
MetaRNN	Uncertain	0.71	D
MetaSVM	Benign	-0.48	T
MutationAssessor	Benign	1.4	L
PrimateAI	Uncertain	0.68	T
PROVEAN	Uncertain	-3.9	D
REVEL	Uncertain	0.43
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.031	D
Polyphen		1.0	D
Vest4		0.54
MutPred		0.62		Loss of stability (P = 0.0304);
MVP		0.66
MPC		0.81
ClinPred		0.98	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.55
gMVP		0.82

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-30435756;