chr12-47236325-G-T

Variant names:

• chr12-47236325-G-T
• rs374835427
• NM_138371.3:c.1262G>T

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.1262G>T​(p.Arg421Ile) 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. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R421T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PCED1B NM_138371.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.278
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19260058).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCED1B	NM_138371.3	c.1262G>T	p.Arg421Ile	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.1262G>T	p.Arg421Ile	missense_variant	Exon 4 of 4	1	NM_138371.3	ENSP00000446688.1
PCED1B	ENST00000432328.2	c.1262G>T	p.Arg421Ile	missense_variant	Exon 3 of 3	3		ENSP00000396040.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.22	T;T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.050	N
LIST_S2	Benign	0.63	.;T
M_CAP	Benign	0.025	D
MetaRNN	Benign	0.19	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	2.0	M;M
PhyloP100		0.28
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-4.0	D;D
REVEL	Benign	0.074
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.018	D;D
Polyphen		0.96	D;D
Vest4		0.29
MutPred		0.38		Gain of catalytic residue at K420 (P = 4e-04);Gain of catalytic residue at K420 (P = 4e-04);
MVP		0.37
MPC		1.5
ClinPred		0.98	D
GERP RS		0.81
Varity_R		0.13
gMVP		0.22
Mutation Taster		=100/0	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: rs374835427; hg19: chr12-47630108;