chr12-47235602-A-G

Variant names:

• chr12-47235602-A-G
• rs934461789
• NM_138371.3:c.539A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_138371.3(PCED1B):​c.539A>G​(p.Lys180Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 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: PCED1B NM_138371.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.77
• Publications: 1 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08903968).

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.539A>G	p.Lys180Arg	missense	Exon 4 of 4	NP_612380.1	Q96HM7
	PCED1B	NM_001281429.2		c.539A>G	p.Lys180Arg	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.539A>G	p.Lys180Arg	missense	Exon 4 of 4	ENSP00000446688.1	Q96HM7
	PCED1B	ENST00000432328.2	TSL:3	c.539A>G	p.Lys180Arg	missense	Exon 3 of 3	ENSP00000396040.1	Q96HM7
	PCED1B	ENST00000872013.1		c.539A>G	p.Lys180Arg	missense	Exon 4 of 4	ENSP00000542072.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

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	Benign	0.072
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	17
DANN	Benign	0.97
DEOGEN2	Benign	0.043	T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.20	T
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.089	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		3.8
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.92	N
REVEL	Benign	0.044
Sift	Benign	0.078	T
Sift4G	Benign	0.18	T
Polyphen		0.022	B
Vest4		0.11
MutPred		0.28		Gain of catalytic residue at F176 (P = 9e-04)
MVP		0.32
MPC		0.33
ClinPred		0.37	T
GERP RS		4.2
Varity_R		0.077
gMVP		0.33
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		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: rs934461789; hg19: chr12-47629385;