rs1214169078

Variant names:

• chr3-53292080-C-T
• rs1214169078
• NM_018403.7:c.1372G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018403.7(DCP1A):​c.1372G>A​(p.Ala458Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,610,340 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: DCP1A NM_018403.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0350
• Publications: 0 publications found

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]

ENSG00000302984 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08149809).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018403.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCP1A	NM_018403.7	MANE Select	c.1372G>A	p.Ala458Thr	missense	Exon 7 of 10	NP_060873.4
	DCP1A	NM_001290204.2		c.1258G>A	p.Ala420Thr	missense	Exon 6 of 9	NP_001277133.1	Q9NPI6-2
	DCP1A	NM_001290205.2		c.1156G>A	p.Ala386Thr	missense	Exon 8 of 11	NP_001277134.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCP1A	ENST00000610213.6	TSL:1 MANE Select	c.1372G>A	p.Ala458Thr	missense	Exon 7 of 10	ENSP00000476386.1	Q9NPI6-1
	DCP1A	ENST00000863998.1		c.1414G>A	p.Ala472Thr	missense	Exon 8 of 11	ENSP00000534057.1
	DCP1A	ENST00000918281.1		c.1369G>A	p.Ala457Thr	missense	Exon 7 of 10	ENSP00000588340.1

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151900 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1458440 Hom.: 0 Cov.: 36 AF XY: 0.00000276 AC XY: 2 AN XY: 725088

African (AFR) AF: 0.00 AC: 0 AN: 33436

American (AMR) AF: 0.00 AC: 0 AN: 44624

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26002

East Asian (EAS) AF: 0.00 AC: 0 AN: 39652

South Asian (SAS) AF: 0.00 AC: 0 AN: 86088

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52476

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5628

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1110294

Other (OTH) AF: 0.00 AC: 0 AN: 60240

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151900 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74204

African (AFR) AF: 0.00 AC: 0 AN: 41306

American (AMR) AF: 0.000131 AC: 2 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68000

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	15
DANN	Benign	0.75
DEOGEN2	Benign	0.015	T
FATHMM_MKL	Benign	0.40	N
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.073	D
MetaRNN	Benign	0.081	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		-0.035
PrimateAI	Benign	0.44	T
Sift4G	Benign	0.13	T
Polyphen		0.044	B
Vest4		0.091
MVP		0.31
GERP RS		1.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.068
gMVP		0.33
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1214169078; hg19: chr3-53326110;