Variant 12-47235968-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_138371.3(PCED1B):c.905T>C(p.Leu302Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,457,544 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

PCED1B
NM_138371.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.389

Variant links:

Genes affected

PCED1B (HGNC:28255): (PC-esterase domain containing 1B) This gene encodes a protein that belongs to the GDSL/SGNH-like acyl-esterase family. Members of this family are hydrolases thought to function in modification of biopolymers on the cell surface. Alternate splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2013]

PCED1B links:

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ACMG classification

Classification made for transcript

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=0.1224207).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCED1B	NM_138371.3 linkuse as main transcript	c.905T>C	p.Leu302Pro	missense_variant	4/4	ENST00000546455.6	NP_612380.1	Q96HM7A0A024R115

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PCED1B	ENST00000546455.6 linkuse as main transcript	c.905T>C	p.Leu302Pro	missense_variant	4/4	1	NM_138371.3	ENSP00000446688.1	Q96HM7
PCED1B	ENST00000432328.2 linkuse as main transcript	c.905T>C	p.Leu302Pro	missense_variant	3/3	3		ENSP00000396040.1	Q96HM7
PCED1B	ENST00000548348.1 linkuse as main transcript	c.545T>C	p.Leu182Pro	missense_variant	2/2	5		ENSP00000448693.1	F8VRF7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000809

AC:

AN:

247342

Hom.:

AF XY:

0.00000746

AC XY:

AN XY:

133962

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000583

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1457544

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

724536

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000449

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

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 submitter

clinical testing

Ambry Genetics

Sep 16, 2021

The c.905T>C (p.L302P) alteration is located in exon 2 (coding exon 1) of the PCED1B gene. This alteration results from a T to C substitution at nucleotide position 905, causing the leucine (L) at amino acid position 302 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

0.071

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.45

CADD

Benign

9.0

DANN

Benign

0.89

DEOGEN2

Benign

0.022

T;T;.

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.63

FATHMM_MKL

Benign

0.054

LIST_S2

Benign

0.28

.;T;T

M_CAP

Benign

0.0080

MetaRNN

Benign

0.12

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.0

N;N;.

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.68

N;N;N

REVEL

Benign

0.18

Sift

Benign

0.33

T;T;T

Sift4G

Benign

0.28

T;T;T

Polyphen

1.0

D;D;.

Vest4

0.19

MutPred

0.28

Gain of catalytic residue at Y299 (P = 0.0025);Gain of catalytic residue at Y299 (P = 0.0025);.;

MVP

0.29

MPC

1.4

ClinPred

0.16

GERP RS

2.0

Varity_R

0.057

gMVP

0.19

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over