20-2836296-C-G

Variant summary

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

The NM_022760.6(PCED1A):ā€‹c.860G>Cā€‹(p.Trp287Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,614,002 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 (ā˜…).

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 32)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

PCED1A
NM_022760.6 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.90
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]

Genome browser will be placed here

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=0.25357565).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PCED1ANM_022760.6 linkuse as main transcriptc.860G>C p.Trp287Ser missense_variant 7/8 ENST00000360652.7 NP_073597.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PCED1AENST00000360652.7 linkuse as main transcriptc.860G>C p.Trp287Ser missense_variant 7/81 NM_022760.6 ENSP00000353868 P1Q9H1Q7-1
PCED1AENST00000356872.7 linkuse as main transcriptc.707G>C p.Trp236Ser missense_variant 7/82 ENSP00000349334 Q9H1Q7-2
PCED1AENST00000474714.5 linkuse as main transcriptc.136-587G>C intron_variant 3 ENSP00000474824
PCED1AENST00000487501.2 linkuse as main transcriptn.245-186G>C intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152174
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000803
AC:
2
AN:
248980
Hom.:
0
AF XY:
0.00000742
AC XY:
1
AN XY:
134794
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000109
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:
1
AN:
1461828
Hom.:
0
Cov.:
35
AF XY:
0.00
AC XY:
0
AN XY:
727206
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
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
AF:
0.00000657
AC:
1
AN:
152174
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74336
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
ExAC
AF:
0.0000165
AC:
2

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 submitterclinical testingAmbry GeneticsMar 01, 2024The c.860G>C (p.W287S) alteration is located in exon 7 (coding exon 6) of the PCED1A gene. This alteration results from a G to C substitution at nucleotide position 860, causing the tryptophan (W) at amino acid position 287 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
0.13
BayesDel_addAF
Benign
-0.26
T
BayesDel_noAF
Benign
-0.38
CADD
Benign
22
DANN
Uncertain
0.98
DEOGEN2
Benign
0.0076
T;.
Eigen
Benign
-0.14
Eigen_PC
Benign
-0.016
FATHMM_MKL
Uncertain
0.78
D
LIST_S2
Benign
0.71
T;T
M_CAP
Benign
0.013
T
MetaRNN
Benign
0.25
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.34
N;.
MutationTaster
Benign
1.0
D;D
PrimateAI
Benign
0.42
T
PROVEAN
Benign
0.45
N;N
REVEL
Benign
0.11
Sift
Benign
0.43
T;T
Sift4G
Benign
0.44
T;T
Polyphen
0.039
B;B
Vest4
0.56
MutPred
0.64
Gain of disorder (P = 0.0023);.;
MVP
0.36
MPC
0.68
ClinPred
0.15
T
GERP RS
3.7
Varity_R
0.14
gMVP
0.47

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.

Other links and lift over

dbSNP: rs773355386; hg19: chr20-2816942; API