NM_144962.3:c.529A>G

Variant names:

• chr8-22713525-T-C
• rs930534797
• NM_144962.3:c.529A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_144962.3(PEBP4):​c.529A>G​(p.Met177Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,613,574 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PEBP4 NM_144962.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.314
• Publications: 0 publications found

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]

EGR3-AS1 (HGNC:58186):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05540204).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144962.3. 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
	PEBP4	NM_144962.3	MANE Select	c.529A>G	p.Met177Val	missense	Exon 7 of 7	NP_659399.2	Q96S96
	PEBP4	NM_001363233.2		c.529A>G	p.Met177Val	missense	Exon 7 of 7	NP_001350162.1	Q96S96

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PEBP4	ENST00000256404.8	TSL:1 MANE Select	c.529A>G	p.Met177Val	missense	Exon 7 of 7	ENSP00000256404.6	Q96S96
	PEBP4	ENST00000901323.1		c.559A>G	p.Met187Val	missense	Exon 8 of 8	ENSP00000571382.1
	PEBP4	ENST00000901324.1		c.529A>G	p.Met177Val	missense	Exon 7 of 7	ENSP00000571383.1

Frequencies

GnomAD3 genomes AF: 0.0000526 AC: 8 AN: 152164 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000193

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461410 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 726998

African (AFR) AF: 0.00 AC: 0 AN: 33456

American (AMR) AF: 0.00 AC: 0 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5746

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111650

Other (OTH) AF: 0.0000331 AC: 2 AN: 60364

GnomAD4 genome AF: 0.0000526 AC: 8 AN: 152164 Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4 AN XY: 74326

African (AFR) AF: 0.000193 AC: 8 AN: 41438

American (AMR) AF: 0.00 AC: 0 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68004

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	3.6
DANN	Benign	0.64
DEOGEN2	Benign	0.00026	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.041	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.0086	T
MetaRNN	Benign	0.055	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.46	N
PhyloP100		-0.31
PrimateAI	Benign	0.35	T
PROVEAN	Benign	0.060	N
REVEL	Benign	0.014
Sift	Benign	0.65	T
Sift4G	Benign	0.55	T
Polyphen		0.090	B
Vest4		0.14
MutPred		0.43		Gain of methylation at K176 (P = 0.0169)
MVP		0.072
MPC		0.018
ClinPred		0.064	T
GERP RS		-2.0
Varity_R		0.032
gMVP		0.34
Mutation Taster		=98/2	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: rs930534797; hg19: chr8-22571038;