Variant 12-47235493-G-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.430G>C(p.Glu144Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,228 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: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

PCED1B
NM_138371.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.09

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=0.10703534).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCED1B	NM_138371.3 linkuse as main transcript	c.430G>C	p.Glu144Gln	missense_variant	4/4	ENST00000546455.6	NP_612380.1	Q96HM7A0A024R115

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCED1B	ENST00000546455.6 linkuse as main transcript	c.430G>C	p.Glu144Gln	missense_variant	4/4	1	NM_138371.3	ENSP00000446688.1		Q96HM7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461228

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726882

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:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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

Nov 17, 2023

The c.430G>C (p.E144Q) alteration is located in exon 2 (coding exon 1) of the PCED1B gene. This alteration results from a G to C substitution at nucleotide position 430, causing the glutamic acid (E) at amino acid position 144 to be replaced by a glutamine (Q). 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

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.071

T;T;.;T;T

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.20

FATHMM_MKL

Benign

0.44

LIST_S2

Benign

0.51

.;T;T;.;T

M_CAP

Benign

0.0031

MetaRNN

Benign

0.11

T;T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

2.0

M;M;.;.;.

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.9

N;N;N;N;N

REVEL

Benign

0.039

Sift

Benign

0.077

T;T;T;T;T

Sift4G

Benign

0.20

T;T;T;T;T

Polyphen

0.15

B;B;.;.;.

Vest4

0.083

MutPred

0.33

Gain of catalytic residue at F147 (P = 0.0784);Gain of catalytic residue at F147 (P = 0.0784);.;Gain of catalytic residue at F147 (P = 0.0784);Gain of catalytic residue at F147 (P = 0.0784);

MVP

0.28

MPC

1.0

ClinPred

0.19

GERP RS

3.4

Varity_R

0.14

gMVP

0.57

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