chr11-126304167-G-T

Position:

chr11-126304167-G-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2

The NM_014026.6(DCPS):c.87G>T(p.Glu29Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000508 in 1,614,276 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00066 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00049 ( 3 hom. )

Consequence

DCPS
NM_014026.6 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:1

Conservation

PhyloP100: 0.593

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 -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0046408176).

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.000493 (720/1461888) while in subpopulation MID AF= 0.0127 (73/5768). AF 95% confidence interval is 0.0103. There are 3 homozygotes in gnomad4_exome. There are 359 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DCPS	NM_014026.6 linkuse as main transcript	c.87G>T	p.Glu29Asp	missense_variant	1/6	ENST00000263579.5
DCPS	NM_001350236.2 linkuse as main transcript	c.87G>T	p.Glu29Asp	missense_variant	1/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
DCPS	ENST00000263579.5 linkuse as main transcript	c.87G>T	p.Glu29Asp	missense_variant	1/6	1	NM_014026.6	P1
TIRAP-AS1	ENST00000524964.2 linkuse as main transcript	n.116+41C>A		intron_variant, non_coding_transcript_variant		2
TIRAP-AS1	ENST00000693424.1 linkuse as main transcript	n.133C>A		non_coding_transcript_exon_variant	1/1
TIRAP-AS1	ENST00000691542.1 linkuse as main transcript	n.114+41C>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.000650

AC:

AN:

152270

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00137

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.000617

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000712

AC:

179

AN:

251372

Hom.:

AF XY:

0.000706

AC XY:

AN XY:

135896

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.00110

Gnomad ASJ exome

AF:

0.00496

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.000633

Gnomad OTH exome

AF:

0.00196

GnomAD4 exome

AF:

0.000493

AC:

720

AN:

1461888

Hom.:

Cov.:

AF XY:

0.000494

AC XY:

359

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.000418

Gnomad4 AMR exome

AF:

0.00119

Gnomad4 ASJ exome

AF:

0.00398

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000232

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000347

Gnomad4 OTH exome

AF:

0.00114

GnomAD4 genome

AF:

0.000656

AC:

100

AN:

152388

Hom.:

Cov.:

AF XY:

0.000671

AC XY:

AN XY:

74518

show subpopulations

Gnomad4 AFR

AF:

0.000144

Gnomad4 AMR

AF:

0.00137

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.000617

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.000772

Hom.:

Bravo

AF:

0.000616

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.000601

AC:

EpiCase

AF:

0.00104

EpiControl

AF:

0.000948

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:1

Uncertain significance, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Feb 02, 2017	- -
Likely benign, criteria provided, single submitter	clinical testing	Invitae	Dec 31, 2019	- -

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 13, 2021

The c.87G>T (p.E29D) alteration is located in exon 1 (coding exon 1) of the DCPS gene. This alteration results from a G to T substitution at nucleotide position 87, causing the glutamic acid (E) at amino acid position 29 to be replaced by an aspartic acid (D). 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

0.081

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.67

CADD

Benign

4.3

DANN

Benign

0.96

DEOGEN2

Benign

0.085

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.081

LIST_S2

Benign

0.48

M_CAP

Benign

0.0034

MetaRNN

Benign

0.0046

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.41

MutationTaster

Benign

1.0

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.35

REVEL

Benign

0.024

Sift

Benign

0.29

Sift4G

Benign

0.43

Polyphen

0.0

Vest4

0.051

MutPred

0.46

Gain of loop (P = 0.0195);

MVP

0.22

MPC

0.10

ClinPred

0.013

GERP RS

-0.63

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.6

Varity_R

0.065

gMVP

0.22

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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