dbSNP rs695029: DCPS:p.Phe63Phe (chr11-126304269-C-T) – ACMG Classification: Benign (-19 pts)

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_014026.6(DCPS):c.189C>T(p.Phe63Phe) 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:3

Conservation

PhyloP100: 1.38

Publications

25 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014026.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DCPS	NM_014026.6	MANE Select	c.189C>T	p.Phe63Phe	synonymous	Exon 1 of 6	NP_054745.1	A0A384MTI8
DCPS	NM_001350236.2		c.189C>T	p.Phe63Phe	synonymous	Exon 1 of 6	NP_001337165.1
TIRAP-AS1	NR_187383.1		n.54G>A		non_coding_transcript_exon	Exon 1 of 2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DCPS	ENST00000263579.5	TSL:1 MANE Select	c.189C>T	p.Phe63Phe	synonymous	Exon 1 of 6	ENSP00000263579.4	Q96C86
DCPS	ENST00000861222.1		c.189C>T	p.Phe63Phe	synonymous	Exon 1 of 6	ENSP00000531281.1
DCPS	ENST00000912051.1		c.189C>T	p.Phe63Phe	synonymous	Exon 1 of 6	ENSP00000582110.1

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

GnomAD2 exomes

AF:

0.280

AC:

70120

AN:

250174

AF XY:

0.276

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 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

African (AFR)

AF:

0.0903

AC:

3022

AN:

33480

American (AMR)

AF:

0.416

AC:

18588

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.233

AC:

6101

AN:

26134

East Asian (EAS)

AF:

0.633

AC:

25135

AN:

39698

South Asian (SAS)

AF:

0.318

AC:

27460

AN:

86256

European-Finnish (FIN)

AF:

0.240

AC:

12824

AN:

53406

Middle Eastern (MID)

AF:

0.215

AC:

1241

AN:

5766

European-Non Finnish (NFE)

AF:

0.202

AC:

224600

AN:

1111994

Other (OTH)

AF:

0.240

AC:

14523

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

14748

29495

44243

58990

73738

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8114

16228

24342

32456

40570

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.208

AC:

31675

AN:

152116

Hom.:

4265

Cov.:

AF XY:

0.220

AC XY:

16334

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.0987

AC:

4097

AN:

41530

American (AMR)

AF:

0.323

AC:

4925

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.230

AC:

799

AN:

3468

East Asian (EAS)

AF:

0.640

AC:

3302

AN:

5156

South Asian (SAS)

AF:

0.323

AC:

1561

AN:

4826

European-Finnish (FIN)

AF:

0.247

AC:

2606

AN:

10566

Middle Eastern (MID)

AF:

0.224

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.202

AC:

13735

AN:

67978

Other (OTH)

AF:

0.216

AC:

458

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1178

2356

3535

4713

5891

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

350

700

1050

1400

1750

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.206

Hom.:

11749

Bravo

AF:

0.214

Asia WGS

AF:

0.442

AC:

1531

AN:

3478

EpiCase

AF:

0.199

EpiControl

AF:

0.203

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Al-Raqad syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.28

CADD

Benign

(source)

DANN

Benign

0.95

PhyloP100

1.4

PromoterAI

-0.015

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over