Variant 11-126304127-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_014026.6(DCPS):c.47A>G(p.Asp16Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,574 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

DCPS
NM_014026.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0400

Variant links:

Genes affected

DCPS (HGNC:29812): (decapping enzyme, scavenger) This gene encodes a member of the histidine triad family of pyrophosphatases that removes short mRNA fragments containing the 5′ mRNA cap structure, which appear in the 3′ → 5′ mRNA decay pathway, following deadenylation and exosome-mediated turnover. This enzyme hydrolyzes the triphosphate linkage of the cap structure (7-methylguanosine nucleoside triphosphate) to yield 7-methylguanosine monophosphate and nucleoside diphosphate. It protects the cell from the potentially toxic accumulation of these short, capped mRNA fragments, and regulates the activity of other cap-binding proteins, which are inhibited by their accumulation. It also acts as a transcript-specific modulator of pre-mRNA splicing and microRNA turnover. [provided by RefSeq, Apr 2017]

DCPS links:

TIRAP-AS1 (HGNC:56069): (TIRAP antisense RNA 1)

TIRAP-AS1 links:

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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=0.055158973).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCPS	NM_014026.6 link	c.47A>G	p.Asp16Gly	missense_variant	Exon 1 of 6	ENST00000263579.5	NP_054745.1	Q96C86A0A384MTI8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DCPS	ENST00000263579.5 link	c.47A>G	p.Asp16Gly	missense_variant	Exon 1 of 6	1	NM_014026.6	ENSP00000263579.4	Q96C86
TIRAP-AS1	ENST00000693424.1 link	n.173T>C		non_coding_transcript_exon_variant	Exon 1 of 1
TIRAP-AS1	ENST00000524964.2 link	n.116+81T>C		intron_variant	Intron 1 of 1	2
TIRAP-AS1	ENST00000691542.1 link	n.114+81T>C		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

250220

Hom.:

AF XY:

0.00000738

AC XY:

AN XY:

135432

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.0000996

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461574

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727060

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000223

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.72

CADD

Benign

5.7

DANN

Benign

0.83

DEOGEN2

Benign

0.077

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.69

M_CAP

Benign

0.0057

MetaRNN

Benign

0.055

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

PrimateAI

Benign

0.40

PROVEAN

Benign

-1.3

REVEL

Benign

0.11

Sift

Uncertain

0.0070

Sift4G

Benign

0.25

Polyphen

0.0

Vest4

0.089

MutPred

0.15

Gain of MoRF binding (P = 0.0381);

MVP

0.085

MPC

0.15

ClinPred

0.057

GERP RS

-5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.070

gMVP

0.29

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over