Variant rs651922 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014026.6(DCPS):c.377-10A>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 1,613,582 control chromosomes in the GnomAD database, including 51,500 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.24 ( 4569 hom., cov: 31)

Exomes 𝑓: 0.25 ( 46931 hom. )

Consequence

DCPS
NM_014026.6 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00006390

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.118

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.257 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCPS	NM_014026.6 linkuse as main transcript	c.377-10A>G		splice_polypyrimidine_tract_variant, intron_variant		ENST00000263579.5	NP_054745.1
DCPS	NM_001350236.2 linkuse as main transcript	c.398-10A>G		splice_polypyrimidine_tract_variant, intron_variant			NP_001337165.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
DCPS	ENST00000263579.5 linkuse as main transcript	c.377-10A>G	splice_polypyrimidine_tract_variant, intron_variant	1	NM_014026.6	ENSP00000263579	P1
DCPS	ENST00000648516.1 linkuse as main transcript	c.98-10A>G	splice_polypyrimidine_tract_variant, intron_variant			ENSP00000497684
DCPS	ENST00000530860.5 linkuse as main transcript		upstream_gene_variant	3

Frequencies

GnomAD3 genomes

AF:

0.245

AC:

37155

AN:

151890

Hom.:

4565

Cov.:

show subpopulations

Gnomad AFR

AF:

0.223

Gnomad AMI

AF:

0.235

Gnomad AMR

AF:

0.263

Gnomad ASJ

AF:

0.254

Gnomad EAS

AF:

0.184

Gnomad SAS

AF:

0.228

Gnomad FIN

AF:

0.239

Gnomad MID

AF:

0.165

Gnomad NFE

AF:

0.260

Gnomad OTH

AF:

0.244

GnomAD3 exomes

AF:

0.242

AC:

60786

AN:

251048

Hom.:

7595

AF XY:

0.240

AC XY:

32612

AN XY:

135694

show subpopulations

Gnomad AFR exome

AF:

0.219

Gnomad AMR exome

AF:

0.281

Gnomad ASJ exome

AF:

0.253

Gnomad EAS exome

AF:

0.176

Gnomad SAS exome

AF:

0.212

Gnomad FIN exome

AF:

0.232

Gnomad NFE exome

AF:

0.253

Gnomad OTH exome

AF:

0.244

GnomAD4 exome

AF:

0.251

AC:

366941

AN:

1461574

Hom.:

46931

Cov.:

AF XY:

0.250

AC XY:

181953

AN XY:

727088

show subpopulations

Gnomad4 AFR exome

AF:

0.218

Gnomad4 AMR exome

AF:

0.273

Gnomad4 ASJ exome

AF:

0.255

Gnomad4 EAS exome

AF:

0.189

Gnomad4 SAS exome

AF:

0.214

Gnomad4 FIN exome

AF:

0.234

Gnomad4 NFE exome

AF:

0.258

Gnomad4 OTH exome

AF:

0.248

GnomAD4 genome

AF:

0.245

AC:

37179

AN:

152008

Hom.:

4569

Cov.:

AF XY:

0.242

AC XY:

17956

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.223

Gnomad4 AMR

AF:

0.264

Gnomad4 ASJ

AF:

0.254

Gnomad4 EAS

AF:

0.184

Gnomad4 SAS

AF:

0.228

Gnomad4 FIN

AF:

0.239

Gnomad4 NFE

AF:

0.260

Gnomad4 OTH

AF:

0.244

Alfa

AF:

0.250

Hom.:

10734

Bravo

AF:

0.242

Asia WGS

AF:

0.220

AC:

767

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

6.1

DANN

Benign

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000064

dbscSNV1_RF

Benign

0.0

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over