Genetic Variant DCP1B:p.Ser543Arg (chr12-1949230-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_152640.5(DCP1B):c.1629C>A(p.Ser543Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,848 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. S543T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

DCP1B
NM_152640.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.941

Publications

0 publications found

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]

DCP1B links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04200974).

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.1629C>A	p.Ser543Arg	missense	Exon 8 of 9	NP_689853.3
	DCP1B	NR_135060.2		n.1781C>A		non_coding_transcript_exon	Exon 9 of 11

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DCP1B	ENST00000280665.11	TSL:1 MANE Select	c.1629C>A	p.Ser543Arg	missense	Exon 8 of 9	ENSP00000280665.6	Q8IZD4-1
DCP1B	ENST00000971563.1		c.1629C>A	p.Ser543Arg	missense	Exon 8 of 10	ENSP00000641622.1
DCP1B	ENST00000883051.1		c.1710C>A	p.Ser570Arg	missense	Exon 8 of 9	ENSP00000553110.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461848

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727220

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.0000348

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53382

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1112010

Other (OTH)

AF:

0.00

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.052

(source)

DANN

Benign

0.60

DEOGEN2

Benign

0.0082

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.048

M_CAP

Benign

0.0054

MetaRNN

Benign

0.042

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.5

PhyloP100

-0.94

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.8

REVEL

Benign

0.0060

Sift

Benign

0.11

Sift4G

Benign

0.17

Polyphen

0.0040

Vest4

0.15

MutPred

0.25

Loss of phosphorylation at S543 (P = 0.007)

MVP

0.088

MPC

0.084

ClinPred

0.037

GERP RS

0.0071

Varity_R

0.033

gMVP

0.24

Mutation Taster

=88/12

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over