3-53292121-G-C

Position:

• chr3-53292121-G-C

Variant summary

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

The NM_018403.7(DCP1A):​c.1331C>G​(p.Ala444Gly) 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. 10/15 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: 1.50

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=0.21544781).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCP1A	NM_018403.7	c.1331C>G	p.Ala444Gly	missense_variant	7/10	ENST00000610213.6	NP_060873.4
LOC107986087	XR_001740702.3	n.208-778G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCP1A	ENST00000610213.6	c.1331C>G	p.Ala444Gly	missense_variant	7/10	1	NM_018403.7	ENSP00000476386	P1
DCP1A	ENST00000294241.10	c.1217C>G	p.Ala406Gly	missense_variant	6/9	2		ENSP00000476046

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

Apr 15, 2024

The c.1331C>G (p.A444G) alteration is located in exon 7 (coding exon 7) of the DCP1A gene. This alteration results from a C to G substitution at nucleotide position 1331, causing the alanine (A) at amino acid position 444 to be replaced by a glycine (G). 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	0.085
BayesDel_addAF	Benign	-0.063	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	12
DANN	Benign	0.72
DEOGEN2	Benign	0.017	T;.
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.77	T;T
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.22	T;T
MutationAssessor	Uncertain	2.2	M;.
PrimateAI	Benign	0.39	T
Sift4G	Benign	0.43	T;T
Polyphen		0.31	B;.
Vest4		0.30
MVP		0.42
GERP RS		0.84
Varity_R		0.034
gMVP		0.37

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: chr3-53326151;