rs1169043795

Variant names:

• chr12-47235883-A-G
• rs1169043795
• NM_138371.3:c.820A>G

Variant summary

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

The NM_138371.3(PCED1B):​c.820A>G​(p.Arg274Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000417 in 1,439,298 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000042 (0 hom.)
• Consequence: PCED1B NM_138371.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.291

Genes affected

PCED1B (HGNC:28255): (PC-esterase domain containing 1B) This gene encodes a protein that belongs to the GDSL/SGNH-like acyl-esterase family. Members of this family are hydrolases thought to function in modification of biopolymers on the cell surface. Alternate splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2013]

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=0.057496816).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCED1B	NM_138371.3	c.820A>G	p.Arg274Gly	missense_variant	Exon 4 of 4	ENST00000546455.6	NP_612380.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCED1B	ENST00000546455.6	c.820A>G	p.Arg274Gly	missense_variant	Exon 4 of 4	1	NM_138371.3	ENSP00000446688.1
PCED1B	ENST00000432328.2	c.820A>G	p.Arg274Gly	missense_variant	Exon 3 of 3	3		ENSP00000396040.1
PCED1B	ENST00000548348.1	c.460A>G	p.Arg154Gly	missense_variant	Exon 2 of 2	5		ENSP00000448693.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000975 AC: 2 AN: 205080 Hom.: 0 AF XY: 0.0000179 AC XY: 2 AN XY: 111592

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000678

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: 0.00000417 AC: 6 AN: 1439298 Hom.: 0 Cov.: 31 AF XY: 0.00000280 AC XY: 2 AN XY: 714274

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000149

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.: 32

Alfa AF: 0.0000508 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Jan 20, 2025

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	2.1
DANN	Benign	0.68
DEOGEN2	Benign	0.015	T;T;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.00089	N
LIST_S2	Benign	0.32	.;T;T
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.057	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;N;.
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.070	N;N;N
REVEL	Benign	0.029
Sift	Benign	0.43	T;T;T
Sift4G	Benign	0.36	T;T;T
Polyphen		0.0	B;B;.
Vest4		0.034
MutPred		0.36		Gain of catalytic residue at K270 (P = 0);Gain of catalytic residue at K270 (P = 0);.;
MVP		0.10
MPC		0.45
ClinPred		0.018	T
GERP RS		-2.8
Varity_R		0.043
gMVP		0.26

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

Other links and lift over

dbSNP: rs1169043795; hg19: chr12-47629666;