20-2839241-A-T

Variant summary

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

The NM_022760.6(PCED1A):c.155T>A(p.Leu52His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: PCED1A NM_022760.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.13

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]

ACMG classification

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	UniProt
PCED1A	NM_022760.6	c.155T>A	p.Leu52His	missense_variant	3/8	ENST00000360652.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCED1A	ENST00000360652.7	c.155T>A	p.Leu52His	missense_variant	3/8	1	NM_022760.6	P1
PCED1A	ENST00000356872.7	c.155T>A	p.Leu52His	missense_variant	3/8	2
PCED1A	ENST00000439542.1	c.155T>A	p.Leu52His	missense_variant	3/6	2
PCED1A	ENST00000448755.5	c.155T>A	p.Leu52His	missense_variant	3/6	3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 31, 2023

The c.155T>A (p.L52H) alteration is located in exon 3 (coding exon 2) of the PCED1A gene. This alteration results from a T to A substitution at nucleotide position 155, causing the leucine (L) at amino acid position 52 to be replaced by a histidine (H). 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	Pathogenic	0.58
BayesDel_addAF	Pathogenic	0.16	D
BayesDel_noAF	Uncertain	-0.010
Cadd	Uncertain	25
Dann	Uncertain	0.98
DEOGEN2	Benign	0.19	T;.;.;.
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.92	D;D;D;D
M_CAP	Benign	0.049	D
MetaRNN	Uncertain	0.48	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	2.9	M;M;.;.
MutationTaster	Benign	0.98	D;D
PrimateAI	Uncertain	0.75	T
PROVEAN	Pathogenic	-5.7	D;D;D;D
REVEL	Benign	0.23
Sift	Benign	0.036	D;D;D;D
Sift4G	Uncertain	0.0040	D;D;.;.
Polyphen		1.0	D;D;.;.
Vest4		0.78
MutPred		0.32		Gain of relative solvent accessibility (P = 0.0479);Gain of relative solvent accessibility (P = 0.0479);Gain of relative solvent accessibility (P = 0.0479);Gain of relative solvent accessibility (P = 0.0479);
MVP		0.33
MPC		1.4
ClinPred		0.99	D
GERP RS		2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.35
gMVP		0.66

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-2819887;