Variant chr11-126306583-C-CTGGGGA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM4BP6_ModerateBS1BS2

The NM_014026.6(DCPS):c.225_230dup(p.Asp76_Gly77dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0177 in 1,608,582 control chromosomes in the GnomAD database, including 384 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.012 ( 20 hom., cov: 31)

Exomes 𝑓: 0.018 ( 364 hom. )

Consequence

DCPS
NM_014026.6 inframe_insertion

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.419

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 -8 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_014026.6.

BP6

Variant 11-126306583-C-CTGGGGA is Benign according to our data. Variant chr11-126306583-C-CTGGGGA is described in ClinVar as [Benign]. Clinvar id is 3068672.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0123 (1875/152182) while in subpopulation SAS AF= 0.0357 (172/4814). AF 95% confidence interval is 0.0314. There are 20 homozygotes in gnomad4. There are 902 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 20 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DCPS	NM_014026.6 linkuse as main transcript	c.225_230dup	p.Asp76_Gly77dup	inframe_insertion	2/6	ENST00000263579.5
DCPS	NM_001350236.2 linkuse as main transcript	c.246_251dup	p.Asp83_Gly84dup	inframe_insertion	2/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCPS	ENST00000263579.5 linkuse as main transcript	c.225_230dup	p.Asp76_Gly77dup	inframe_insertion	2/6	1	NM_014026.6	P1

Frequencies

GnomAD3 genomes

AF:

0.0123

AC:

1876

AN:

152064

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00273

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00544

Gnomad ASJ

AF:

0.0309

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0353

Gnomad FIN

AF:

0.0121

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0182

Gnomad OTH

AF:

0.0124

GnomAD3 exomes

AF:

0.0173

AC:

4283

AN:

247900

Hom.:

AF XY:

0.0190

AC XY:

2552

AN XY:

134122

show subpopulations

Gnomad AFR exome

AF:

0.00229

Gnomad AMR exome

AF:

0.00552

Gnomad ASJ exome

AF:

0.0314

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0392

Gnomad FIN exome

AF:

0.0125

Gnomad NFE exome

AF:

0.0196

Gnomad OTH exome

AF:

0.0180

GnomAD4 exome

AF:

0.0183

AC:

26676

AN:

1456400

Hom.:

364

Cov.:

AF XY:

0.0192

AC XY:

13923

AN XY:

723458

show subpopulations

Gnomad4 AFR exome

AF:

0.00222

Gnomad4 AMR exome

AF:

0.00541

Gnomad4 ASJ exome

AF:

0.0305

Gnomad4 EAS exome

AF:

0.000127

Gnomad4 SAS exome

AF:

0.0411

Gnomad4 FIN exome

AF:

0.0144

Gnomad4 NFE exome

AF:

0.0180

Gnomad4 OTH exome

AF:

0.0192

GnomAD4 genome

AF:

0.0123

AC:

1875

AN:

152182

Hom.:

Cov.:

AF XY:

0.0121

AC XY:

902

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.00272

Gnomad4 AMR

AF:

0.00543

Gnomad4 ASJ

AF:

0.0309

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0357

Gnomad4 FIN

AF:

0.0121

Gnomad4 NFE

AF:

0.0182

Gnomad4 OTH

AF:

0.0123

Alfa

AF:

0.0186

Hom.:

Asia WGS

AF:

0.0150

AC:

AN:

3478

EpiCase

AF:

0.0189

EpiControl

AF:

0.0180

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Al-Raqad syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Molecular Genetics, Royal Melbourne Hospital

May 04, 2023

South Asian population allele frequency is 3.731% (rs201095573,1185/30256 alleles, 32 homozygotes in gnomAD v2.1). Based on the classification scheme RMH Modified ACMG/AMP Guidelines v1.5.1, this variant is classified as BENIGN. Following criteria are met: BA1 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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