Menu
GeneBe

chr12-2004352-T-C

Variant summary

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

The NM_152640.5(DCP1B):ā€‹c.80A>Gā€‹(p.Tyr27Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000018 in 1,613,216 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000013 ( 0 hom., cov: 32)
Exomes š‘“: 0.000018 ( 0 hom. )

Consequence

DCP1B
NM_152640.5 missense

Scores

6
8
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.55
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
DCP1BNM_152640.5 linkuse as main transcriptc.80A>G p.Tyr27Cys missense_variant 1/9 ENST00000280665.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
DCP1BENST00000280665.11 linkuse as main transcriptc.80A>G p.Tyr27Cys missense_variant 1/91 NM_152640.5 P1Q8IZD4-1

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152226
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000161
AC:
4
AN:
248504
Hom.:
0
AF XY:
0.00000741
AC XY:
1
AN XY:
135006
show subpopulations
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 SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000269
Gnomad OTH exome
AF:
0.000165
GnomAD4 exome
AF:
0.0000185
AC:
27
AN:
1460990
Hom.:
0
Cov.:
31
AF XY:
0.0000151
AC XY:
11
AN XY:
726826
show subpopulations
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:
0.0000190
Gnomad4 NFE exome
AF:
0.0000216
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152226
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74366
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.0000113
ExAC
AF:
0.0000165
AC:
2
EpiCase
AF:
0.00
EpiControl
AF:
0.000178

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsAug 08, 2022The c.80A>G (p.Y27C) alteration is located in exon 1 (coding exon 1) of the DCP1B gene. This alteration results from a A to G substitution at nucleotide position 80, causing the tyrosine (Y) at amino acid position 27 to be replaced by a cysteine (C). 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
Pathogenic
0.58
BayesDel_addAF
Pathogenic
0.18
D
BayesDel_noAF
Uncertain
0.090
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.094
T;.
Eigen
Pathogenic
0.72
Eigen_PC
Pathogenic
0.69
FATHMM_MKL
Benign
0.32
N
M_CAP
Uncertain
0.19
D
MetaRNN
Uncertain
0.69
D;D
MetaSVM
Benign
-0.88
T
MutationAssessor
Uncertain
2.2
M;.
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Pathogenic
0.83
D
PROVEAN
Pathogenic
-7.7
D;.
REVEL
Uncertain
0.59
Sift
Uncertain
0.011
D;.
Sift4G
Uncertain
0.0030
D;D
Polyphen
1.0
D;D
Vest4
0.65
MutPred
0.72
Gain of catalytic residue at P26 (P = 5e-04);Gain of catalytic residue at P26 (P = 5e-04);
MVP
0.39
MPC
0.15
ClinPred
0.97
D
GERP RS
5.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.77
gMVP
0.76

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs777121803; hg19: chr12-2113518; API