Variant chr11-126304269-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_014026.6(DCPS):c.189C>T(p.Phe63=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 1,613,960 control chromosomes in the GnomAD database, including 48,037 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 4265 hom., cov: 32)

Exomes 𝑓: 0.23 ( 43772 hom. )

Consequence

DCPS
NM_014026.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.38

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.28).

BP6

Variant 11-126304269-C-T is Benign according to our data. Variant chr11-126304269-C-T is described in ClinVar as [Benign]. Clinvar id is 1229675.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.38 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.622 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DCPS	NM_014026.6 linkuse as main transcript	c.189C>T	p.Phe63=	synonymous_variant	1/6	ENST00000263579.5
DCPS	NM_001350236.2 linkuse as main transcript	c.189C>T	p.Phe63=	synonymous_variant	1/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
DCPS	ENST00000263579.5 linkuse as main transcript	c.189C>T	p.Phe63=	synonymous_variant	1/6	1	NM_014026.6	P1
TIRAP-AS1	ENST00000524964.2 linkuse as main transcript	n.55G>A		non_coding_transcript_exon_variant	1/2	2
TIRAP-AS1	ENST00000691542.1 linkuse as main transcript	n.53G>A		non_coding_transcript_exon_variant	1/2
TIRAP-AS1	ENST00000693424.1 linkuse as main transcript	n.31G>A		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes

AF:

0.208

AC:

31669

AN:

151996

Hom.:

4263

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0988

Gnomad AMI

AF:

0.138

Gnomad AMR

AF:

0.322

Gnomad ASJ

AF:

0.230

Gnomad EAS

AF:

0.641

Gnomad SAS

AF:

0.323

Gnomad FIN

AF:

0.247

Gnomad MID

AF:

0.231

Gnomad NFE

AF:

0.202

Gnomad OTH

AF:

0.217

GnomAD3 exomes

AF:

0.280

AC:

70120

AN:

250174

Hom.:

12330

AF XY:

0.276

AC XY:

37422

AN XY:

135378

show subpopulations

Gnomad AFR exome

AF:

0.0978

Gnomad AMR exome

AF:

0.428

Gnomad ASJ exome

AF:

0.237

Gnomad EAS exome

AF:

0.649

Gnomad SAS exome

AF:

0.318

Gnomad FIN exome

AF:

0.237

Gnomad NFE exome

AF:

0.204

Gnomad OTH exome

AF:

0.257

GnomAD4 exome

AF:

0.228

AC:

333494

AN:

1461844

Hom.:

43772

Cov.:

AF XY:

0.230

AC XY:

167403

AN XY:

727220

show subpopulations

Gnomad4 AFR exome

AF:

0.0903

Gnomad4 AMR exome

AF:

0.416

Gnomad4 ASJ exome

AF:

0.233

Gnomad4 EAS exome

AF:

0.633

Gnomad4 SAS exome

AF:

0.318

Gnomad4 FIN exome

AF:

0.240

Gnomad4 NFE exome

AF:

0.202

Gnomad4 OTH exome

AF:

0.240

GnomAD4 genome

AF:

0.208

AC:

31675

AN:

152116

Hom.:

4265

Cov.:

AF XY:

0.220

AC XY:

16334

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.0987

Gnomad4 AMR

AF:

0.323

Gnomad4 ASJ

AF:

0.230

Gnomad4 EAS

AF:

0.640

Gnomad4 SAS

AF:

0.323

Gnomad4 FIN

AF:

0.247

Gnomad4 NFE

AF:

0.202

Gnomad4 OTH

AF:

0.216

Alfa

AF:

0.205

Hom.:

7107

Bravo

AF:

0.214

Asia WGS

AF:

0.442

AC:

1531

AN:

3478

EpiCase

AF:

0.199

EpiControl

AF:

0.203

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Al-Raqad syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 16, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Benign

0.95

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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