12-47235085-G-A

Position:

• chr12-47235085-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_138371.3(PCED1B):​c.22G>A​(p.Glu8Lys) 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. 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: 3.50

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39514756).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCED1B	NM_138371.3	c.22G>A	p.Glu8Lys	missense_variant	4/4	ENST00000546455.6	NP_612380.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCED1B	ENST00000546455.6	c.22G>A	p.Glu8Lys	missense_variant	4/4	1	NM_138371.3	ENSP00000446688.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 29, 2021

The c.22G>A (p.E8K) alteration is located in exon 2 (coding exon 1) of the PCED1B gene. This alteration results from a G to A substitution at nucleotide position 22, causing the glutamic acid (E) at amino acid position 8 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.62
BayesDel_addAF	Benign	-0.096	T
BayesDel_noAF	Benign	-0.38
CADD	Pathogenic	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.31	T;T;T;T;.
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.94	.;D;.;D;D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.40	T;T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.7	M;M;.;.;.
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-2.9	D;D;D;D;D
REVEL	Benign	0.17
Sift	Uncertain	0.0060	D;D;D;D;D
Sift4G	Uncertain	0.012	D;D;D;D;D
Polyphen		0.99	D;D;.;.;.
Vest4		0.51
MutPred		0.35		Gain of MoRF binding (P = 1e-04);Gain of MoRF binding (P = 1e-04);Gain of MoRF binding (P = 1e-04);Gain of MoRF binding (P = 1e-04);Gain of MoRF binding (P = 1e-04);
MVP		0.51
MPC		1.1
ClinPred		0.96	D
GERP RS		4.1
Varity_R		0.27
gMVP		0.42

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-47628868; COSMIC: COSV71395065; COSMIC: COSV71395065;