NM_138371.3:c.44A>G

Variant names:

• chr12-47235107-A-G
• NM_138371.3:c.44A>G
• PCED1B p.Asn15Ser

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_138371.3(PCED1B):​c.44A>G​(p.Asn15Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000029 in 1,377,978 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000029 (0 hom.)
• Consequence: PCED1B NM_138371.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.11
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138371.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCED1B	NM_138371.3	MANE Select	c.44A>G	p.Asn15Ser	missense	Exon 4 of 4	NP_612380.1	Q96HM7
	PCED1B	NM_001281429.2		c.44A>G	p.Asn15Ser	missense	Exon 3 of 3	NP_001268358.1	Q96HM7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCED1B	ENST00000546455.6	TSL:1 MANE Select	c.44A>G	p.Asn15Ser	missense	Exon 4 of 4	ENSP00000446688.1	Q96HM7
	PCED1B	ENST00000432328.2	TSL:3	c.44A>G	p.Asn15Ser	missense	Exon 3 of 3	ENSP00000396040.1	Q96HM7
	PCED1B	ENST00000872013.1		c.44A>G	p.Asn15Ser	missense	Exon 4 of 4	ENSP00000542072.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000290 AC: 4 AN: 1377978 Hom.: 0 Cov.: 30 AF XY: 0.00000443 AC XY: 3 AN XY: 676604

African (AFR) AF: 0.00 AC: 0 AN: 30716

American (AMR) AF: 0.0000316 AC: 1 AN: 31630

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20312

East Asian (EAS) AF: 0.0000257 AC: 1 AN: 38986

South Asian (SAS) AF: 0.00 AC: 0 AN: 71800

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50088

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5350

European-Non Finnish (NFE) AF: 0.00000187 AC: 2 AN: 1072358

Other (OTH) AF: 0.00 AC: 0 AN: 56738

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.45	T
Eigen	Pathogenic	0.68
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.028	D
MetaRNN	Uncertain	0.49	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		5.1
PrimateAI	Uncertain	0.63	T
PROVEAN	Pathogenic	-4.4	D
REVEL	Benign	0.28
Sift	Uncertain	0.0040	D
Sift4G	Pathogenic	0.0	D
Varity_R		0.38
gMVP		0.54
Mutation Taster		=83/17	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr12-47628890;