NM_152640.5:c.7G>A

Variant names:

• chr12-2004425-C-T
• rs539589278
• NM_152640.5:c.7G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152640.5(DCP1B):​c.7G>A​(p.Ala3Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 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. A3P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DCP1B NM_152640.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.80
• Publications: 4 publications found

Genes affected

DCP1B (HGNC:24451): (decapping mRNA 1B) This gene encodes a member of a family of proteins that function in removing the 5' cap from mRNAs, which is a step in regulated mRNA decay. This protein localizes to cytoplasmic foci which are the site of mRNA breakdown and turnover. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

CACNA1C (HGNC:1390): (calcium voltage-gated channel subunit alpha1 C) This gene encodes an alpha-1 subunit of a voltage-dependent calcium channel. Calcium channels mediate the influx of calcium ions into the cell upon membrane polarization. The alpha-1 subunit consists of 24 transmembrane segments and forms the pore through which ions pass into the cell. The calcium channel consists of a complex of alpha-1, alpha-2/delta, beta, and gamma subunits in a 1:1:1:1 ratio. There are multiple isoforms of each of these proteins, either encoded by different genes or the result of alternative splicing of transcripts. The protein encoded by this gene binds to and is inhibited by dihydropyridine. Alternative splicing results in many transcript variants encoding different proteins. Some of the predicted proteins may not produce functional ion channel subunits. [provided by RefSeq, Oct 2012]

CACNA1C Gene-Disease associations (from GenCC):

• Timothy syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, Orphanet
• neurodevelopmental disorder with hypotonia, language delay, and skeletal defects with or without seizures

  Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics
• long QT syndrome

  Inheritance: AD Classification: MODERATE Submitted by: ClinGen
• long QT syndrome 8

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
• Brugada syndrome

  Inheritance: AD Classification: SUPPORTIVE, NO_KNOWN Submitted by: ClinGen, Orphanet
• Brugada syndrome 3

  Inheritance: AD Classification: LIMITED, NO_KNOWN Submitted by: Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• intellectual disability

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• short QT syndrome

  Inheritance: AD Classification: LIMITED, NO_KNOWN Submitted by: ClinGen, Ambry Genetics

ENSG00000203593 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15589854).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152640.5. 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
	DCP1B	NM_152640.5	MANE Select	c.7G>A	p.Ala3Thr	missense	Exon 1 of 9	NP_689853.3
	DCP1B	NM_001319292.2		c.7G>A	p.Ala3Thr	missense	Exon 1 of 3	NP_001306221.1	B4DVJ6
	DCP1B	NR_135060.2		n.33G>A		non_coding_transcript_exon	Exon 1 of 11

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCP1B	ENST00000280665.11	TSL:1 MANE Select	c.7G>A	p.Ala3Thr	missense	Exon 1 of 9	ENSP00000280665.6	Q8IZD4-1
	CACNA1C	ENST00000682544.1		c.139+33224C>T		intron	N/A	ENSP00000507184.1	A0A804HIR0
	CACNA1C	ENST00000683824.1		c.139+33224C>T		intron	N/A	ENSP00000507867.1	A0A804HKC4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000411 AC: 1 AN: 243212 AF XY: 0.00000756

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000923

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1456624 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 724334

African (AFR) AF: 0.00 AC: 0 AN: 33422

American (AMR) AF: 0.00 AC: 0 AN: 44500

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25858

East Asian (EAS) AF: 0.00 AC: 0 AN: 39652

South Asian (SAS) AF: 0.00 AC: 0 AN: 85524

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52256

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5192

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110060

Other (OTH) AF: 0.00 AC: 0 AN: 60160

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000826 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Benign	-0.0065	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.015	T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.17
FATHMM_MKL	Benign	0.52	D
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PhyloP100		4.8
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-0.81	N
REVEL	Benign	0.078
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.011	D
Polyphen		0.44	B
Vest4		0.26
MutPred		0.30		Gain of catalytic residue at G8 (P = 0)
MVP		0.31
MPC		0.071
ClinPred		0.79	D
GERP RS		3.7
PromoterAI		-0.54	Under-expression
Varity_R		0.13
gMVP		0.55
Mutation Taster		=88/12	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: rs539589278; hg19: chr12-2113591;