rs35836343

Positions:

chr11-126343347-G-A

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_014026.6(DCPS):c.677G>A(p.Gly226Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00491 in 1,613,898 control chromosomes in the GnomAD database, including 40 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0040 ( 9 hom., cov: 31)

Exomes 𝑓: 0.0050 ( 31 hom. )

Consequence

DCPS
NM_014026.6 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.49

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:

GSEC (HGNC:48645): (G-quadruplex forming sequence containing lncRNA)

GSEC links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012222111).

BP6

Variant 11-126343347-G-A is Benign according to our data. Variant chr11-126343347-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 376909.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-126343347-G-A is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
DCPS	NM_014026.6 linkuse as main transcript	c.677G>A	p.Gly226Asp	missense_variant	5/6	ENST00000263579.5
GSEC	NR_033839.1 linkuse as main transcript	n.147-1025C>T		intron_variant, non_coding_transcript_variant
DCPS	NM_001350236.2 linkuse as main transcript	c.698G>A	p.Gly233Asp	missense_variant	5/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCPS	ENST00000263579.5 linkuse as main transcript	c.677G>A	p.Gly226Asp	missense_variant	5/6	1	NM_014026.6	P1
GSEC	ENST00000629441.3 linkuse as main transcript	n.147-1025C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00400

AC:

609

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000869

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00190

Gnomad ASJ

AF:

0.0363

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000848

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00588

Gnomad OTH

AF:

0.00431

GnomAD3 exomes

AF:

0.00447

AC:

1121

AN:

250816

Hom.:

AF XY:

0.00441

AC XY:

598

AN XY:

135626

show subpopulations

Gnomad AFR exome

AF:

0.000864

Gnomad AMR exome

AF:

0.00156

Gnomad ASJ exome

AF:

0.0332

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000164

Gnomad FIN exome

AF:

0.000556

Gnomad NFE exome

AF:

0.00591

Gnomad OTH exome

AF:

0.00523

GnomAD4 exome

AF:

0.00500

AC:

7313

AN:

1461656

Hom.:

Cov.:

AF XY:

0.00505

AC XY:

3673

AN XY:

727110

show subpopulations

Gnomad4 AFR exome

AF:

0.000896

Gnomad4 AMR exome

AF:

0.00161

Gnomad4 ASJ exome

AF:

0.0314

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000313

Gnomad4 FIN exome

AF:

0.000712

Gnomad4 NFE exome

AF:

0.00540

Gnomad4 OTH exome

AF:

0.00507

GnomAD4 genome

AF:

0.00400

AC:

609

AN:

152242

Hom.:

Cov.:

AF XY:

0.00356

AC XY:

265

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.000866

Gnomad4 AMR

AF:

0.00190

Gnomad4 ASJ

AF:

0.0363

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000848

Gnomad4 NFE

AF:

0.00588

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00663

Hom.:

Bravo

AF:

0.00429

TwinsUK

AF:

0.00809

AC:

ALSPAC

AF:

0.00597

AC:

ESP6500AA

AF:

0.00114

AC:

ESP6500EA

AF:

0.00768

AC:

ExAC

AF:

0.00396

AC:

481

EpiCase

AF:

0.00589

EpiControl

AF:

0.00611

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Invitae	Dec 31, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Jul 13, 2016	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Apr 01, 2024	DCPS: BP4, BS2 -

Inborn genetic diseases

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 18, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

DCPS-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 07, 2020

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Al-Raqad syndrome

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Mendelics

May 28, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.15

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Uncertain

0.69

D;.

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.77

T;T

M_CAP

Benign

0.056

MetaRNN

Benign

0.012

T;T

MetaSVM

Benign

-0.53

MutationAssessor

Benign

-0.17

N;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.44

PROVEAN

Uncertain

-3.7

D;.

REVEL

Uncertain

0.38

Sift

Benign

0.27

T;.

Sift4G

Benign

0.60

T;.

Polyphen

0.018

B;.

Vest4

0.33

MVP

0.68

MPC

0.15

ClinPred

0.023

GERP RS

0.20

Varity_R

0.43

gMVP

0.77

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