11-126304269-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_014026.6(DCPS):c.189C>T(p.Phe63=) 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.38

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]

TIRAP-AS1 (HGNC:56069): (TIRAP antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DCPS	NM_014026.6	c.189C>T	p.Phe63=	synonymous_variant	1/6	ENST00000263579.5
DCPS	NM_001350236.2	c.189C>T	p.Phe63=	synonymous_variant	1/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCPS	ENST00000263579.5	c.189C>T	p.Phe63=	synonymous_variant	1/6	1	NM_014026.6	P1
TIRAP-AS1	ENST00000524964.2	n.55G>A		non_coding_transcript_exon_variant	1/2	2
TIRAP-AS1	ENST00000691542.1	n.53G>A		non_coding_transcript_exon_variant	1/2
TIRAP-AS1	ENST00000693424.1	n.31G>A		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31669 AN: 151996 Hom.: 4263 Cov.: 32

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

GnomAD3 exomes AF: 0.280 AC: 70120 AN: 250174 Hom.: 12330 AF XY: 0.276 AC XY: 37422 AN XY: 135378

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 SAS exome AF: 0.318

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.: 35 AF XY: 0.230 AC XY: 167403 AN XY: 727220

Gnomad4 AFR exome AF: 0.0903

Gnomad4 AMR exome AF: 0.416

Gnomad4 ASJ exome AF: 0.233

Gnomad4 EAS exome AF: 0.633

Gnomad4 SAS exome AF: 0.318

Gnomad4 FIN exome AF: 0.240

Gnomad4 NFE exome AF: 0.202

Gnomad4 OTH exome AF: 0.240

GnomAD4 genome AF: 0.208 AC: 31675 AN: 152116 Hom.: 4265 Cov.: 32 AF XY: 0.220 AC XY: 16334 AN XY: 74366

Gnomad4 AFR AF: 0.0987

Gnomad4 AMR AF: 0.323

Gnomad4 ASJ AF: 0.230

Gnomad4 EAS AF: 0.640

Gnomad4 SAS AF: 0.323

Gnomad4 FIN AF: 0.247

Gnomad4 NFE AF: 0.202

Gnomad4 OTH AF: 0.216

Alfa AF: 0.205 Hom.: 7107

Bravo AF: 0.214

Asia WGS AF: 0.442 AC: 1531 AN: 3478

EpiCase AF: 0.199

EpiControl AF: 0.203

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Al-Raqad syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 16, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
Cadd	Benign	18
Dann	Benign	0.95

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

LitVar

Other links and lift over

dbSNP: rs695029; hg19: chr11-126174164; COSMIC: COSV55012080;