3-53292112-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_018403.7(DCP1A):c.1340C>T(p.Ala447Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00326 in 1,613,578 control chromosomes in the GnomAD database, including 228 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0056 (32 hom., cov: 32)
  • Exomes 𝑓: 0.0030 (196 hom.)
• Consequence: DCP1A NM_018403.7 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.333

Genes affected

DCP1A (HGNC:18714): (decapping mRNA 1A) Decapping is a key step in general and regulated mRNA decay. The protein encoded by this gene is a decapping enzyme. This protein and another decapping enzyme form a decapping complex, which interacts with the nonsense-mediated decay factor hUpf1 and may be recruited to mRNAs containing premature termination codons. This protein also participates in the TGF-beta signaling pathway. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Feb 2014]

LOC107986087 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0023297668).
• BP6: Variant 3-53292112-G-A is Benign according to our data. Variant chr3-53292112-G-A is described in ClinVar as [Benign]. Clinvar id is 770142.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0799 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DCP1A	NM_018403.7	c.1340C>T	p.Ala447Val	missense_variant	7/10	ENST00000610213.6
LOC107986087	XR_001740702.3	n.208-787G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCP1A	ENST00000610213.6	c.1340C>T	p.Ala447Val	missense_variant	7/10	1	NM_018403.7	P1
DCP1A	ENST00000294241.10	c.1226C>T	p.Ala409Val	missense_variant	6/9	2

Frequencies

GnomAD3 genomes AF: 0.00552 AC: 839 AN: 151934 Hom.: 29 Cov.: 32

Gnomad AFR AF: 0.00160

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0471

Gnomad ASJ AF: 0.00116

Gnomad EAS AF: 0.00560

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000946

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00527

GnomAD3 exomes AF: 0.0125 AC: 3100 AN: 248746 Hom.: 156 AF XY: 0.00958 AC XY: 1293 AN XY: 134930

Gnomad AFR exome AF: 0.00123

Gnomad AMR exome AF: 0.0853

Gnomad ASJ exome AF: 0.000398

Gnomad EAS exome AF: 0.00390

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000798

Gnomad OTH exome AF: 0.00894

GnomAD4 exome AF: 0.00302 AC: 4413 AN: 1461526 Hom.: 196 Cov.: 34 AF XY: 0.00264 AC XY: 1918 AN XY: 727032

Gnomad4 AFR exome AF: 0.000986

Gnomad4 AMR exome AF: 0.0821

Gnomad4 ASJ exome AF: 0.000459

Gnomad4 EAS exome AF: 0.0122

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000459

Gnomad4 OTH exome AF: 0.00265

GnomAD4 genome AF: 0.00559 AC: 850 AN: 152052 Hom.: 32 Cov.: 32 AF XY: 0.00603 AC XY: 448 AN XY: 74332

Gnomad4 AFR AF: 0.00159

Gnomad4 AMR AF: 0.0478

Gnomad4 ASJ AF: 0.00116

Gnomad4 EAS AF: 0.00562

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000946

Gnomad4 NFE AF: 0.000147

Gnomad4 OTH AF: 0.00522

Alfa AF: 0.000800 Hom.: 4

Bravo AF: 0.00956

ESP6500AA AF: 0.000962 AC: 4

ESP6500EA AF: 0.000356 AC: 3

ExAC AF: 0.00905 AC: 1096

Asia WGS AF: 0.00375 AC: 13 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000296

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 30, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.54
Cadd	Benign	6.4
Dann	Benign	0.73
DEOGEN2	Benign	0.016	T;.
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.70	T;T
MetaRNN	Benign	0.0023	T;T
MutationAssessor	Benign	1.1	L;.
PrimateAI	Benign	0.38	T
Sift4G	Benign	0.58	T;T
Polyphen		0.0	B;.
Vest4		0.16
GERP RS		0.73
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.055
gMVP		0.31

Splicing

Name	Calibrated prediction	Score	Prediction
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

Other links and lift over

dbSNP: rs143190624; hg19: chr3-53326142; COSMIC: COSV53691406; COSMIC: COSV53691406;