8-22724851-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_144962.3(PEBP4):ā€‹c.509A>Gā€‹(p.Lys170Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,612,828 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. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000041 ( 0 hom. )

Consequence

PEBP4
NM_144962.3 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.365
Variant links:
Genes affected
PEBP4 (HGNC:28319): (phosphatidylethanolamine binding protein 4) The phosphatidylethanolamine (PE)-binding proteins, including PEBP4, are an evolutionarily conserved family of proteins with pivotal biologic functions, such as lipid binding and inhibition of serine proteases (Wang et al., 2004 [PubMed 15302887]).[supplied by OMIM, Dec 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.042750925).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PEBP4NM_144962.3 linkc.509A>G p.Lys170Arg missense_variant 6/7 ENST00000256404.8 NP_659399.2 Q96S96
PEBP4NM_001363233.2 linkc.509A>G p.Lys170Arg missense_variant 6/7 NP_001350162.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PEBP4ENST00000256404.8 linkc.509A>G p.Lys170Arg missense_variant 6/71 NM_144962.3 ENSP00000256404.6 Q96S96
ENSG00000253125ENST00000523627.1 linkn.165-19743T>C intron_variant 4

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152218
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000802
AC:
2
AN:
249504
Hom.:
0
AF XY:
0.00000739
AC XY:
1
AN XY:
135382
show subpopulations
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:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000177
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000411
AC:
6
AN:
1460610
Hom.:
0
Cov.:
30
AF XY:
0.00000413
AC XY:
3
AN XY:
726754
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152218
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74368
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378
ExAC
AF:
0.00000827
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsAug 11, 2024The c.509A>G (p.K170R) alteration is located in exon 6 (coding exon 5) of the PEBP4 gene. This alteration results from a A to G substitution at nucleotide position 509, causing the lysine (K) at amino acid position 170 to be replaced by an arginine (R). 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
Benign
0.082
BayesDel_addAF
Benign
-0.37
T
BayesDel_noAF
Benign
-0.75
CADD
Benign
2.6
DANN
Benign
0.89
DEOGEN2
Benign
0.0027
T
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.025
N
LIST_S2
Benign
0.43
T
M_CAP
Benign
0.0089
T
MetaRNN
Benign
0.043
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.6
L
PrimateAI
Benign
0.32
T
PROVEAN
Benign
-0.69
N
REVEL
Benign
0.0090
Sift
Benign
0.33
T
Sift4G
Benign
0.30
T
Polyphen
0.065
B
Vest4
0.078
MutPred
0.29
Loss of methylation at K170 (P = 0.0334);
MVP
0.095
MPC
0.017
ClinPred
0.040
T
GERP RS
-1.6
Varity_R
0.031
gMVP
0.30

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs753091074; hg19: chr8-22582364; API