3-53292295-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018403.7(DCP1A):c.1157G>C(p.Gly386Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 11/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DCP1A NM_018403.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.04

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.105219424).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DCP1A	NM_018403.7	c.1157G>C	p.Gly386Ala	missense_variant	7/10	ENST00000610213.6
LOC107986087	XR_001740702.3	n.208-604C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCP1A	ENST00000610213.6	c.1157G>C	p.Gly386Ala	missense_variant	7/10	1	NM_018403.7	P1
DCP1A	ENST00000294241.10	c.1043G>C	p.Gly348Ala	missense_variant	6/9	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 22, 2021

The c.1157G>C (p.G386A) alteration is located in exon 7 (coding exon 7) of the DCP1A gene. This alteration results from a G to C substitution at nucleotide position 1157, causing the glycine (G) at amino acid position 386 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
Cadd	Benign	15
Dann	Benign	0.70
DEOGEN2	Benign	0.020	T;.
FATHMM_MKL	Benign	0.40	N
LIST_S2	Benign	0.73	T;T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.11	T;T
MutationAssessor	Benign	1.4	L;.
PrimateAI	Benign	0.29	T
Sift4G	Uncertain	0.037	D;D
Polyphen		0.0	B;.
Vest4		0.15
MVP		0.30
GERP RS		3.6
Varity_R		0.075
gMVP		0.26

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-53326325;