Genetic Variant PAFAH1B3:p.Glu56Lys (chr19-42301952-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_002573.4(PAFAH1B3):c.166G>A(p.Glu56Lys) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PAFAH1B3
NM_002573.4 missense, splice_region

Scores

Splicing: ADA: 0.007946

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.95

Publications

0 publications found

Variant links:

Genes affected

PAFAH1B3 (HGNC:8576): (platelet activating factor acetylhydrolase 1b catalytic subunit 3) This gene encodes an acetylhydrolase that catalyzes the removal of an acetyl group from the glycerol backbone of platelet-activating factor. The encoded enzyme is a subunit of the platelet-activating factor acetylhydrolase isoform 1B complex, which consists of the catalytic beta and gamma subunits and the regulatory alpha subunit. This complex functions in brain development. A translocation between this gene on chromosome 19 and the CDC-like kinase 2 gene on chromosome 1 has been observed, and was associated with cognitive disability, ataxia, and atrophy of the brain. Alternatively spliced transcript variants have been described. [provided by RefSeq, Mar 2009]

PAFAH1B3 links:

PRR19 (HGNC:33728): (proline rich 19)

PRR19 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002573.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PAFAH1B3	NM_002573.4	MANE Select	c.166G>A	p.Glu56Lys	missense splice_region	Exon 2 of 5	NP_002564.1	Q15102
PAFAH1B3	NM_001145939.2		c.166G>A	p.Glu56Lys	missense splice_region	Exon 3 of 6	NP_001139411.1	A0A024R0L6
PAFAH1B3	NM_001145940.1		c.166G>A	p.Glu56Lys	missense splice_region	Exon 3 of 6	NP_001139412.1	Q15102

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PAFAH1B3	ENST00000262890.8	TSL:1 MANE Select	c.166G>A	p.Glu56Lys	missense splice_region	Exon 2 of 5	ENSP00000262890.2	Q15102
PAFAH1B3	ENST00000538771.5	TSL:2	c.166G>A	p.Glu56Lys	missense splice_region	Exon 3 of 6	ENSP00000444935.1	Q15102
PAFAH1B3	ENST00000877854.1		c.166G>A	p.Glu56Lys	missense splice_region	Exon 3 of 6	ENSP00000547913.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1404452

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

693458

African (AFR)

AF:

0.00

AC:

AN:

31834

American (AMR)

AF:

0.00

AC:

AN:

36262

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25228

East Asian (EAS)

AF:

0.00

AC:

AN:

36142

South Asian (SAS)

AF:

0.00

AC:

AN:

79546

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5568

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1081996

Other (OTH)

AF:

0.00

AC:

AN:

58270

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.71

BayesDel_addAF

Benign

-0.065

BayesDel_noAF

Benign

-0.33

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.49

Eigen

Benign

0.14

Eigen_PC

Benign

0.11

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.018

MetaRNN

Uncertain

0.50

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

PhyloP100

6.9

PrimateAI

Uncertain

0.76

PROVEAN

Uncertain

-2.6

REVEL

Benign

0.23

Sift

Uncertain

0.012

Sift4G

Benign

0.18

Polyphen

0.99

Vest4

0.30

MutPred

0.53

Gain of methylation at E56 (P = 0.0017)

MVP

0.69

MPC

0.94

ClinPred

0.98

GERP RS

2.5

PromoterAI

0.0046

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.30

gMVP

0.60

Mutation Taster

=69/31

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0079

dbscSNV1_RF

Benign

0.24

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over