3-53347498-G-C

Variant names:

• chr3-53347498-G-C
• rs1553693321
• NM_018403.7:c.20C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_018403.7(DCP1A):​c.20C>G​(p.Ala7Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,008 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: DCP1A NM_018403.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.00

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]

CACNA1D (HGNC:1391): (calcium voltage-gated channel subunit alpha1 D) Voltage-dependent calcium channels mediate the entry of calcium ions into excitable cells, and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, and gene expression. Calcium channels are multisubunit complexes composed of alpha-1, beta, alpha-2/delta, and gamma subunits. The channel activity is directed by the pore-forming alpha-1 subunit, whereas the others act as auxiliary subunits regulating this activity. The distinctive properties of the calcium channel types are related primarily to the expression of a variety of alpha-1 isoforms, namely alpha-1A, B, C, D, E, and S. This gene encodes the alpha-1D subunit. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2012]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39313808).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCP1A	NM_018403.7	c.20C>G	p.Ala7Gly	missense_variant	Exon 1 of 10	ENST00000610213.6	NP_060873.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCP1A	ENST00000610213.6	c.20C>G	p.Ala7Gly	missense_variant	Exon 1 of 10	1	NM_018403.7	ENSP00000476386.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460008 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726332

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 30, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.20C>G (p.A7G) alteration is located in exon 1 (coding exon 1) of the DCP1A gene. This alteration results from a C to G substitution at nucleotide position 20, causing the alanine (A) at amino acid position 7 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	Uncertain	0.40
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Uncertain	24
DANN	Benign	0.91
DEOGEN2	Benign	0.067	T;.;.;.
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.85	T;D;D;D
M_CAP	Uncertain	0.17	D
MetaRNN	Benign	0.39	T;T;T;T
MutationAssessor	Benign	1.8	L;L;.;.
PrimateAI	Uncertain	0.61	T
Sift4G	Pathogenic	0.0	D;D;T;.
Polyphen		1.0	D;.;.;.
Vest4		0.43
MVP		0.73
GERP RS		5.2
Varity_R		0.44
gMVP		0.38

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1553693321; hg19: chr3-53381525;