12-47235955-A-C

Variant names:

• chr12-47235955-A-C
• rs752052648
• NM_138371.3:c.892A>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_138371.3(PCED1B):​c.892A>C​(p.Thr298Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 16/22 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. T298A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000091 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000021 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PCED1B NM_138371.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.055286318).

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.892A>C	p.Thr298Pro	missense	Exon 4 of 4	NP_612380.1	Q96HM7
	PCED1B	NM_001281429.2		c.892A>C	p.Thr298Pro	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.892A>C	p.Thr298Pro	missense	Exon 4 of 4	ENSP00000446688.1	Q96HM7
	PCED1B	ENST00000432328.2	TSL:3	c.892A>C	p.Thr298Pro	missense	Exon 3 of 3	ENSP00000396040.1	Q96HM7
	PCED1B	ENST00000872013.1		c.892A>C	p.Thr298Pro	missense	Exon 4 of 4	ENSP00000542072.1

Frequencies

GnomAD3 genomes AF: 0.0000913 AC: 12 AN: 131404 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000875

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000772

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000119

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000115

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000207 AC: 3 AN: 1449380 Hom.: 0 Cov.: 32 AF XY: 0.00000278 AC XY: 2 AN XY: 720554

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33176

American (AMR) AF: 0.00 AC: 0 AN: 43910

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25742

East Asian (EAS) AF: 0.00 AC: 0 AN: 39158

South Asian (SAS) AF: 0.00 AC: 0 AN: 85582

European-Finnish (FIN) AF: 0.0000193 AC: 1 AN: 51726

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5700

European-Non Finnish (NFE) AF: 0.00000181 AC: 2 AN: 1104770

Other (OTH) AF: 0.00 AC: 0 AN: 59616

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000913 AC: 12 AN: 131490 Hom.: 0 Cov.: 31 AF XY: 0.0000944 AC XY: 6 AN XY: 63578

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000872 AC: 3 AN: 34394

American (AMR) AF: 0.0000771 AC: 1 AN: 12970

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3204

East Asian (EAS) AF: 0.00 AC: 0 AN: 4452

South Asian (SAS) AF: 0.00 AC: 0 AN: 4034

European-Finnish (FIN) AF: 0.000119 AC: 1 AN: 8436

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 272

European-Non Finnish (NFE) AF: 0.000115 AC: 7 AN: 61118

Other (OTH) AF: 0.00 AC: 0 AN: 1784

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00206 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.047
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	0.049
DANN	Benign	0.53
DEOGEN2	Benign	0.015	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.28	T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.055	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		-1.4
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.12	N
REVEL	Benign	0.018
Sift	Benign	0.34	T
Sift4G	Benign	0.32	T
Polyphen		0.0	B
Vest4		0.058
MutPred		0.24		Gain of catalytic residue at L294 (P = 0)
MVP		0.076
MPC		0.48
ClinPred		0.16	T
GERP RS		-3.4
Varity_R		0.11
gMVP		0.10
Mutation Taster		=96/4	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: rs752052648; hg19: chr12-47629738;