20-2838454-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_022760.6(PCED1A):​c.619C>T​(p.Arg207Trp) variant causes a missense change. The variant allele was found at a frequency of 0.00000616 in 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

PCED1A
NM_022760.6 missense

Scores

4
11
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.17
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 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.787

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PCED1ANM_022760.6 linkuse as main transcriptc.619C>T p.Arg207Trp missense_variant 6/8 ENST00000360652.7 NP_073597.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PCED1AENST00000360652.7 linkuse as main transcriptc.619C>T p.Arg207Trp missense_variant 6/81 NM_022760.6 ENSP00000353868 P1Q9H1Q7-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.0000119
AC:
3
AN:
251310
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135850
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:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000616
AC:
9
AN:
1461874
Hom.:
0
Cov.:
40
AF XY:
0.00000550
AC XY:
4
AN XY:
727242
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:
0.0000116
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.00000540
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000378
ExAC
AF:
0.00000824
AC:
1
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 submitterclinical testingAmbry GeneticsJun 24, 2022The c.619C>T (p.R207W) alteration is located in exon 6 (coding exon 5) of the PCED1A gene. This alteration results from a C to T substitution at nucleotide position 619, causing the arginine (R) at amino acid position 207 to be replaced by a tryptophan (W). 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
0.25
BayesDel_addAF
Uncertain
0.064
T
BayesDel_noAF
Uncertain
-0.060
CADD
Pathogenic
29
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.28
T;.;.;.
Eigen
Uncertain
0.68
Eigen_PC
Uncertain
0.61
FATHMM_MKL
Uncertain
0.89
D
LIST_S2
Uncertain
0.86
D;D;D;T
M_CAP
Uncertain
0.087
D
MetaRNN
Pathogenic
0.79
D;D;D;D
MetaSVM
Benign
-0.88
T
MutationAssessor
Uncertain
2.4
M;.;.;.
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.56
T
PROVEAN
Pathogenic
-6.5
D;D;D;D
REVEL
Uncertain
0.35
Sift
Uncertain
0.0010
D;D;D;D
Sift4G
Pathogenic
0.0010
D;D;.;.
Polyphen
1.0
D;D;.;.
Vest4
0.72
MutPred
0.60
Loss of solvent accessibility (P = 0.0299);.;.;Loss of solvent accessibility (P = 0.0299);
MVP
0.47
MPC
1.2
ClinPred
0.97
D
GERP RS
4.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.62
gMVP
0.88

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.090
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: rs771637059; hg19: chr20-2819100; COSMIC: COSV62313705; COSMIC: COSV62313705; API