rs897453

Variant summary

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

The NM_148172.3(PEMT):​c.283G>T​(p.Val95Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000753 in 1,461,438 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: 31)
Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

PEMT
NM_148172.3 missense

Scores

1
18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0210
Variant links:
Genes affected
PEMT (HGNC:8830): (phosphatidylethanolamine N-methyltransferase) Phosphatidylcholine (PC) is the most abundant mammalian phospholipid. This gene encodes an enzyme which converts phosphatidylethanolamine to phosphatidylcholine by sequential methylation in the liver. Another distinct synthetic pathway in nucleated cells converts intracellular choline to phosphatidylcholine by a three-step process. The protein isoforms encoded by this gene localize to the endoplasmic reticulum and mitochondria-associated membranes. Alternate splicing of this gene results in multiple transcript variants encoding different isoforms. [provided by RefSeq, May 2012]

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=0.05570835).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PEMTNM_148172.3 linkuse as main transcriptc.283G>T p.Val95Phe missense_variant 3/7 ENST00000255389.10 NP_680477.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PEMTENST00000255389.10 linkuse as main transcriptc.283G>T p.Val95Phe missense_variant 3/71 NM_148172.3 ENSP00000255389 Q9UBM1-2

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD3 exomes
AF:
0.00000799
AC:
2
AN:
250372
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135494
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000580
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000753
AC:
11
AN:
1461438
Hom.:
0
Cov.:
36
AF XY:
0.00000413
AC XY:
3
AN XY:
727032
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000447
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:
0.00000810
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.083
BayesDel_addAF
Benign
-0.34
T
BayesDel_noAF
Benign
-0.55
CADD
Benign
0.33
DANN
Benign
0.88
DEOGEN2
Benign
0.14
T;T;.;.;.
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.5
FATHMM_MKL
Benign
0.022
N
LIST_S2
Uncertain
0.90
.;D;D;D;D
M_CAP
Benign
0.0032
T
MetaRNN
Benign
0.056
T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.13
N;N;.;.;.
MutationTaster
Benign
1.0
P;P;P;P;P
PrimateAI
Benign
0.28
T
PROVEAN
Benign
-1.8
N;N;N;N;N
REVEL
Benign
0.046
Sift
Benign
0.48
T;T;T;T;T
Sift4G
Benign
0.37
T;T;T;T;T
Polyphen
0.0010
B;B;.;B;.
Vest4
0.18
MutPred
0.20
Loss of catalytic residue at V58 (P = 0.0982);Loss of catalytic residue at V58 (P = 0.0982);.;.;.;
MVP
0.048
MPC
0.11
ClinPred
0.017
T
GERP RS
-5.1
Varity_R
0.057
gMVP
0.59

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

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

Other links and lift over

dbSNP: rs897453; hg19: chr17-17425631; API