12-1952489-G-A

Position:

• chr12-1952489-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152640.5(DCP1B):​c.1451C>T​(p.Ser484Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DCP1B NM_152640.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.79

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15330571).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCP1B	NM_152640.5	c.1451C>T	p.Ser484Phe	missense_variant	7/9	ENST00000280665.11	NP_689853.3
DCP1B	NR_135060.2	n.1603C>T		non_coding_transcript_exon_variant	8/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCP1B	ENST00000280665.11	c.1451C>T	p.Ser484Phe	missense_variant	7/9	1	NM_152640.5	ENSP00000280665.6
DCP1B	ENST00000540622.1	c.1073C>T	p.Ser358Phe	missense_variant	4/5	5		ENSP00000444374.1
DCP1B	ENST00000543381.5	n.*1217C>T		non_coding_transcript_exon_variant	8/10	5		ENSP00000445011.1
DCP1B	ENST00000543381.5	n.*1217C>T		3_prime_UTR_variant	8/10	5		ENSP00000445011.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 04, 2024

The c.1451C>T (p.S484F) alteration is located in exon 7 (coding exon 7) of the DCP1B gene. This alteration results from a C to T substitution at nucleotide position 1451, causing the serine (S) at amino acid position 484 to be replaced by a phenylalanine (F). 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	Benign	0.11
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.020	T;.
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.38	N
M_CAP	Benign	0.0093	T
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L;.
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.7	N;D
REVEL	Benign	0.079
Sift	Uncertain	0.015	D;D
Sift4G	Benign	0.065	T;T
Polyphen		0.85	P;.
Vest4		0.31
MutPred		0.34		Gain of catalytic residue at K488 (P = 0.0041);.;
MVP		0.30
MPC		0.16
ClinPred		0.57	D
GERP RS		3.8
Varity_R		0.060
gMVP		0.18

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-2061655;