Variant chr20-2835549-C-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_022760.6(PCED1A):c.1278G>T(p.Arg426Ser) 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 1,461,838 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

PCED1A
NM_022760.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.647

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCED1A	NM_022760.6 linkuse as main transcript	c.1278G>T	p.Arg426Ser	missense_variant	8/8	ENST00000360652.7	NP_073597.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCED1A	ENST00000360652.7 linkuse as main transcript	c.1278G>T	p.Arg426Ser	missense_variant	8/8	1	NM_022760.6	ENSP00000353868	P1	Q9H1Q7-1
PCED1A	ENST00000356872.7 linkuse as main transcript	c.1125G>T	p.Arg375Ser	missense_variant	8/8	2		ENSP00000349334		Q9H1Q7-2
PCED1A	ENST00000474714.5 linkuse as main transcript	c.297G>T	p.Arg99Ser	missense_variant	2/2	3		ENSP00000474824
PCED1A	ENST00000487501.2 linkuse as main transcript	n.477G>T		non_coding_transcript_exon_variant	4/4	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251080

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135710

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

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:

6.84e-7

AC:

AN:

1461838

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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

Jun 16, 2024

The c.1278G>T (p.R426S) alteration is located in exon 8 (coding exon 7) of the PCED1A gene. This alteration results from a G to T substitution at nucleotide position 1278, causing the arginine (R) at amino acid position 426 to be replaced by a serine (S). 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

0.27

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.058

T;.

Eigen

Benign

-0.079

Eigen_PC

Benign

-0.19

FATHMM_MKL

Benign

0.30

LIST_S2

Benign

0.82

T;T

M_CAP

Benign

0.064

MetaRNN

Uncertain

0.48

T;T

MetaSVM

Benign

-0.78

MutationAssessor

Uncertain

2.3

M;.

MutationTaster

Benign

0.86

D;D

PrimateAI

Benign

0.42

PROVEAN

Benign

-1.8

N;N

REVEL

Benign

0.22

Sift

Uncertain

0.010

D;D

Sift4G

Uncertain

0.040

D;D

Polyphen

0.99

D;D

Vest4

0.46

MutPred

0.60

Loss of catalytic residue at R426 (P = 0.0245);.;

MVP

0.46

MPC

1.3

ClinPred

0.86

GERP RS

0.70

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.13

gMVP

0.37

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