12-1949259-T-G

Variant names:

• chr12-1949259-T-G
• rs753450583
• NM_152640.5:c.1600A>C

Variant summary

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

The NM_152640.5(DCP1B):​c.1600A>C​(p.Thr534Pro) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: DCP1B NM_152640.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.144

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]

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=0.12441355).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCP1B	NM_152640.5	c.1600A>C	p.Thr534Pro	missense_variant	Exon 8 of 9	ENST00000280665.11	NP_689853.3
DCP1B	NR_135060.2	n.1752A>C		non_coding_transcript_exon_variant	Exon 9 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCP1B	ENST00000280665.11	c.1600A>C	p.Thr534Pro	missense_variant	Exon 8 of 9	1	NM_152640.5	ENSP00000280665.6
DCP1B	ENST00000543381.5	n.*1366A>C		non_coding_transcript_exon_variant	Exon 9 of 10	5		ENSP00000445011.1
DCP1B	ENST00000543381.5	n.*1366A>C		3_prime_UTR_variant	Exon 9 of 10	5		ENSP00000445011.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 25, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1600A>C (p.T534P) alteration is located in exon 8 (coding exon 8) of the DCP1B gene. This alteration results from a A to C substitution at nucleotide position 1600, causing the threonine (T) at amino acid position 534 to be replaced by a proline (P). 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	0.068
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	10
DANN	Benign	0.78
DEOGEN2	Benign	0.013	T
Eigen	Benign	-0.87
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.35	N
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.12
Sift	Uncertain	0.0040	D
Sift4G	Benign	0.13	T
Polyphen		0.93	P
Vest4		0.14
MutPred		0.22		Gain of catalytic residue at P537 (P = 0.001);
MVP		0.21
MPC		0.10
ClinPred		0.64	D
GERP RS		-3.0
Varity_R		0.12
gMVP		0.16

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

Other links and lift over

dbSNP: rs753450583; hg19: chr12-2058425;