chr12-47235896-C-G

Variant names:

• chr12-47235896-C-G
• rs759303227
• NM_138371.3:c.833C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_138371.3(PCED1B):​c.833C>G​(p.Pro278Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000691 in 1,446,788 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: PCED1B NM_138371.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.429

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.045648754).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCED1B	NM_138371.3	c.833C>G	p.Pro278Arg	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.833C>G	p.Pro278Arg	missense_variant	Exon 4 of 4	1	NM_138371.3	ENSP00000446688.1
PCED1B	ENST00000432328.2	c.833C>G	p.Pro278Arg	missense_variant	Exon 3 of 3	3		ENSP00000396040.1
PCED1B	ENST00000548348.1	c.473C>G	p.Pro158Arg	missense_variant	Exon 2 of 2	5		ENSP00000448693.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000464 AC: 1 AN: 215748 Hom.: 0 AF XY: 0.00000852 AC XY: 1 AN XY: 117304

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000349

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.91e-7 AC: 1 AN: 1446788 Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1 AN XY: 718574

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000118

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000829 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.21
DANN	Benign	0.42
DEOGEN2	Benign	0.017	T;T;.
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0085	N
LIST_S2	Benign	0.34	.;T;T
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.046	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.83	L;L;.
PrimateAI	Benign	0.26	T
PROVEAN	Benign	1.2	N;N;N
REVEL	Benign	0.0040
Sift	Benign	0.65	T;T;T
Sift4G	Benign	0.93	T;T;T
Polyphen		0.0	B;B;.
Vest4		0.087
MutPred		0.40		Gain of MoRF binding (P = 0.0029);Gain of MoRF binding (P = 0.0029);.;
MVP		0.048
MPC		0.37
ClinPred		0.0095	T
GERP RS		-3.0
Varity_R		0.025
gMVP		0.19

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

LitVar

Other links and lift over

dbSNP: rs759303227; hg19: chr12-47629679;