Variant 20-2836092-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_022760.6(PCED1A):c.1064A>G(p.His355Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000148 in 1,348,050 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 0.0000015 ( 0 hom. )

Consequence

PCED1A
NM_022760.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0470

Variant links:

Genes affected

PCED1A (HGNC:16212): (PC-esterase domain containing 1A) The protein encoded by this gene is a member of the GDSL/SGNH superfamily. Members of this family are hydrolytic enzymes with esterase and lipase activity and broad substrate specificity. This protein belongs to the Pmr5-Cas1p-esterase subfamily in that it contains the catalytic triad comprised of serine, aspartate and histidine and lacks two conserved regions (glycine after strand S2 and GxND motif). A pseudogene of this gene has been identified on the long arm of chromosome 2. Alternative splicing results in multiple transcript variants that encode different protein isoforms. [provided by RefSeq, Sep 2012]

PCED1A links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.066868246).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCED1A	NM_022760.6 linkuse as main transcript	c.1064A>G	p.His355Arg	missense_variant	7/8	ENST00000360652.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCED1A	ENST00000360652.7 linkuse as main transcript	c.1064A>G	p.His355Arg	missense_variant	7/8	1	NM_022760.6	P1	Q9H1Q7-1
PCED1A	ENST00000356872.7 linkuse as main transcript	c.911A>G	p.His304Arg	missense_variant	7/8	2			Q9H1Q7-2
PCED1A	ENST00000474714.5 linkuse as main transcript	c.136-383A>G		intron_variant		3
PCED1A	ENST00000487501.2 linkuse as main transcript	n.263A>G		non_coding_transcript_exon_variant	3/4	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000637

AC:

AN:

156878

Hom.:

AF XY:

0.00

AC XY:

AN XY:

81982

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000459

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:

0.00000148

AC:

AN:

1348050

Hom.:

Cov.:

AF XY:

0.00000151

AC XY:

AN XY:

663564

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000321

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:

9.50e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Dec 12, 2022

The c.1064A>G (p.H355R) alteration is located in exon 7 (coding exon 6) of the PCED1A gene. This alteration results from a A to G substitution at nucleotide position 1064, causing the histidine (H) at amino acid position 355 to be replaced by an arginine (R). 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

0.059

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.54

Cadd

Benign

Dann

Benign

0.79

DEOGEN2

Benign

0.012

T;.

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.44

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.64

T;T

M_CAP

Benign

0.0069

MetaRNN

Benign

0.067

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

L;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.46

N;N

REVEL

Benign

0.014

Sift

Benign

0.064

T;T

Sift4G

Benign

0.62

T;T

Polyphen

0.013

B;B

Vest4

0.12

MutPred

0.29

Gain of solvent accessibility (P = 0.0704);.;

MVP

0.29

MPC

0.52

ClinPred

0.023

GERP RS

0.067

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.2

Varity_R

0.035

gMVP

0.16

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

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