chr3-53338051-G-A

Variant names:

• chr3-53338051-G-A
• rs9311496
• NM_018403.7:c.304+4093C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018403.7(DCP1A):​c.304+4093C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00895 in 356,980 control chromosomes in the GnomAD database, including 94 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.018 (87 hom., cov: 32)
  • Exomes 𝑓: 0.0022 (7 hom.)
• Consequence: DCP1A NM_018403.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.686
• Publications: 1 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]

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]

CACNA1D Gene-Disease associations (from GenCC):

• aldosterone-producing adenoma with seizures and neurological abnormalities

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Illumina, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• sinoatrial node dysfunction and deafness

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet, ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0608 is higher than 0.05.

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.304+4093C>T		intron	N/A	NP_060873.4
	DCP1A	NM_001290204.2		c.304+4093C>T		intron	N/A	NP_001277133.1	Q9NPI6-2
	DCP1A	NM_001290205.2		c.88+40C>T		intron	N/A	NP_001277134.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCP1A	ENST00000610213.6	TSL:1 MANE Select	c.304+4093C>T		intron	N/A	ENSP00000476386.1	Q9NPI6-1
	CACNA1D	ENST00000637424.1	TSL:5	c.139+8607G>A		intron	N/A	ENSP00000489769.1	A0A1B0GTN0
	DCP1A	ENST00000863998.1		c.304+4093C>T		intron	N/A	ENSP00000534057.1

Frequencies

GnomAD3 genomes AF: 0.0180 AC: 2740 AN: 152084 Hom.: 86 Cov.: 32

Gnomad AFR AF: 0.0629

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.0115

GnomAD4 exome AF: 0.00220 AC: 450 AN: 204778 Hom.: 7 Cov.: 0 AF XY: 0.00184 AC XY: 212 AN XY: 115424

African (AFR) AF: 0.0567 AC: 325 AN: 5728

American (AMR) AF: 0.00422 AC: 67 AN: 15864

Ashkenazi Jewish (ASJ) AF: 0.000163 AC: 1 AN: 6140

East Asian (EAS) AF: 0.00 AC: 0 AN: 7958

South Asian (SAS) AF: 0.000177 AC: 8 AN: 45190

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9152

Middle Eastern (MID) AF: 0.00147 AC: 1 AN: 678

European-Non Finnish (NFE) AF: 0.0000478 AC: 5 AN: 104550

Other (OTH) AF: 0.00452 AC: 43 AN: 9518

GnomAD4 genome AF: 0.0180 AC: 2745 AN: 152202 Hom.: 87 Cov.: 32 AF XY: 0.0175 AC XY: 1306 AN XY: 74420

African (AFR) AF: 0.0628 AC: 2609 AN: 41518

American (AMR) AF: 0.00654 AC: 100 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

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

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68008

Other (OTH) AF: 0.0114 AC: 24 AN: 2112

Alfa AF: 0.00606 Hom.: 29

Bravo AF: 0.0200

Asia WGS AF: 0.00404 AC: 14 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.39
DANN	Benign	0.64
PhyloP100		-0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs9311496; hg19: chr3-53372078;