rs782383240

Variant names:

• chr3-53292125-C-G
• rs782383240
• NM_018403.7:c.1327G>C

Your query was ambiguous. Multiple possible variants found:

• chr3-53292125-C-G
• chr3-53292125-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_018403.7(DCP1A):​c.1327G>C​(p.Ala443Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,666 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 9/14 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A443T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: DCP1A NM_018403.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.318
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32701743).

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.1327G>C	p.Ala443Pro	missense	Exon 7 of 10	NP_060873.4
	DCP1A	NM_001290204.2		c.1213G>C	p.Ala405Pro	missense	Exon 6 of 9	NP_001277133.1	Q9NPI6-2
	DCP1A	NM_001290205.2		c.1111G>C	p.Ala371Pro	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.1327G>C	p.Ala443Pro	missense	Exon 7 of 10	ENSP00000476386.1	Q9NPI6-1
	DCP1A	ENST00000863998.1		c.1369G>C	p.Ala457Pro	missense	Exon 8 of 11	ENSP00000534057.1
	DCP1A	ENST00000918281.1		c.1324G>C	p.Ala442Pro	missense	Exon 7 of 10	ENSP00000588340.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461666 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 727112

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53366

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111862

Other (OTH) AF: 0.00 AC: 0 AN: 60372

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Uncertain	0.070	D
BayesDel_noAF	Benign	-0.14
CADD	Benign	17
DANN	Benign	0.74
DEOGEN2	Benign	0.017	T
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.080	D
MetaRNN	Benign	0.33	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		0.32
PrimateAI	Benign	0.44	T
Sift4G	Benign	0.30	T
Polyphen		0.0	B
Vest4		0.46
MVP		0.49
GERP RS		3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.19
gMVP		0.42
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs782383240; hg19: chr3-53326155;