NM_138371.3:c.362T>G

Variant names:

• chr12-47235425-T-G
• rs1592334461
• NM_138371.3:c.362T>G

Variant summary

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

The NM_138371.3(PCED1B):​c.362T>G​(p.Met121Arg) 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: 33)
• Consequence: PCED1B NM_138371.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.55
• 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.362T>G	p.Met121Arg	missense	Exon 4 of 4	NP_612380.1	Q96HM7
	PCED1B	NM_001281429.2		c.362T>G	p.Met121Arg	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.362T>G	p.Met121Arg	missense	Exon 4 of 4	ENSP00000446688.1	Q96HM7
	PCED1B	ENST00000548348.1	TSL:5	c.2T>G	p.Met1?	start_lost	Exon 2 of 2	ENSP00000448693.1	F8VRF7
	PCED1B	ENST00000432328.2	TSL:3	c.362T>G	p.Met121Arg	missense	Exon 3 of 3	ENSP00000396040.1	Q96HM7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	Pathogenic	0.92
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.33	T
Eigen	Pathogenic	0.69
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.010	T
MetaRNN	Uncertain	0.62	D
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		6.5
PrimateAI	Uncertain	0.51	T
PROVEAN	Pathogenic	-5.3	D
REVEL	Uncertain	0.37
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.99	D
Vest4		0.83
MutPred		0.47		Gain of catalytic residue at L125 (P = 0)
MVP		0.54
MPC		1.4
ClinPred		0.99	D
GERP RS		4.4
Varity_R		0.93
gMVP		0.91
Mutation Taster		=56/44	polymorphism

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

Other links and lift over

dbSNP: rs1592334461; hg19: chr12-47629208;