20-2836225-G-A

Position:

• chr20-2836225-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_022760.6(PCED1A):​c.931C>T​(p.Leu311Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 32)
• Consequence: PCED1A NM_022760.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.15

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 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=0.051769793).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCED1A	NM_022760.6	c.931C>T	p.Leu311Phe	missense_variant	7/8	ENST00000360652.7	NP_073597.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCED1A	ENST00000360652.7	c.931C>T	p.Leu311Phe	missense_variant	7/8	1	NM_022760.6	ENSP00000353868	P1
PCED1A	ENST00000356872.7	c.778C>T	p.Leu260Phe	missense_variant	7/8	2		ENSP00000349334
PCED1A	ENST00000474714.5	c.136-516C>T		intron_variant		3		ENSP00000474824
PCED1A	ENST00000487501.2	n.245-115C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

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

Nov 02, 2023

The c.931C>T (p.L311F) alteration is located in exon 7 (coding exon 6) of the PCED1A gene. This alteration results from a C to T substitution at nucleotide position 931, causing the leucine (L) at amino acid position 311 to be replaced by a phenylalanine (F). 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	0.077
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	13
DANN	Benign	0.77
DEOGEN2	Benign	0.0098	T;.
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.40	T;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.052	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.86	N;N
REVEL	Benign	0.024
Sift	Benign	0.62	T;T
Sift4G	Benign	0.70	T;T
Polyphen		0.0	B;B
Vest4		0.097
MutPred		0.26		Loss of catalytic residue at L311 (P = 0.0674);.;
MVP		0.32
MPC		0.44
ClinPred		0.067	T
GERP RS		2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.039
gMVP		0.13

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: chr20-2816871;