Variant chr3-53292080-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_018403.7(DCP1A):c.1372G>A(p.Ala458Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,610,340 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/15 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: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

DCP1A
NM_018403.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0350

Variant links:

Genes affected

DCP1A (HGNC:18714): (decapping mRNA 1A) Decapping is a key step in general and regulated mRNA decay. The protein encoded by this gene is a decapping enzyme. This protein and another decapping enzyme form a decapping complex, which interacts with the nonsense-mediated decay factor hUpf1 and may be recruited to mRNAs containing premature termination codons. This protein also participates in the TGF-beta signaling pathway. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Feb 2014]

DCP1A links:

LOC107986087 (HGNC:):

LOC107986087 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=0.08149809).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCP1A	NM_018403.7 linkuse as main transcript	c.1372G>A	p.Ala458Thr	missense_variant	7/10	ENST00000610213.6	NP_060873.4	Q9NPI6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCP1A	ENST00000610213.6 linkuse as main transcript	c.1372G>A	p.Ala458Thr	missense_variant	7/10	1	NM_018403.7	ENSP00000476386.1		Q9NPI6-1
DCP1A	ENST00000294241.10 linkuse as main transcript	c.1258G>A	p.Ala420Thr	missense_variant	6/9	2		ENSP00000476046.2		Q9NPI6-2

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151900

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.00

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1458440

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

725088

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151900

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74204

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

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:

0.00

Bravo

AF:

0.00000756

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

Nov 11, 2024

The c.1372G>A (p.A458T) alteration is located in exon 7 (coding exon 7) of the DCP1A gene. This alteration results from a G to A substitution at nucleotide position 1372, causing the alanine (A) at amino acid position 458 to be replaced by a threonine (T). 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

0.073

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.75

DEOGEN2

Benign

0.015

T;.

FATHMM_MKL

Benign

0.40

LIST_S2

Benign

0.79

T;T

M_CAP

Benign

0.073

MetaRNN

Benign

0.081

T;T

MutationAssessor

Uncertain

2.1

M;.

PrimateAI

Benign

0.44

Sift4G

Benign

0.13

T;T

Polyphen

0.044

B;.

Vest4

0.091

MVP

0.31

GERP RS

1.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.068

gMVP

0.33

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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