rs779901301

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_148172.3(PEMT):​c.212G>C​(p.Arg71Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000685 in 1,459,262 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R71Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)
Exomes š‘“: 0.0000069 ( 0 hom. )

Consequence

PEMT
NM_148172.3 missense

Scores

6
9
4

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.32
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_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.979

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PEMTNM_148172.3 linkc.212G>C p.Arg71Pro missense_variant Exon 3 of 7 ENST00000255389.10 NP_680477.1 Q9UBM1-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PEMTENST00000255389.10 linkc.212G>C p.Arg71Pro missense_variant Exon 3 of 7 1 NM_148172.3 ENSP00000255389.5 Q9UBM1-2

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD3 exomes
AF:
0.00000799
AC:
2
AN:
250310
Hom.:
0
AF XY:
0.00000738
AC XY:
1
AN XY:
135560
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:
0.00000685
AC:
10
AN:
1459262
Hom.:
0
Cov.:
32
AF XY:
0.00000826
AC XY:
6
AN XY:
726152
show subpopulations
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000811
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
31
Bravo
AF:
0.00000378
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.76
BayesDel_addAF
Pathogenic
0.25
D
BayesDel_noAF
Uncertain
0.13
CADD
Pathogenic
28
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.60
D;D;.;.;.
Eigen
Pathogenic
0.70
Eigen_PC
Uncertain
0.58
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.96
.;D;D;D;D
M_CAP
Benign
0.025
D
MetaRNN
Pathogenic
0.98
D;D;D;D;D
MetaSVM
Benign
-0.40
T
MutationAssessor
Pathogenic
3.2
M;M;.;.;.
PrimateAI
Benign
0.46
T
PROVEAN
Pathogenic
-6.5
D;D;D;D;D
REVEL
Uncertain
0.64
Sift
Uncertain
0.0010
D;D;D;D;D
Sift4G
Uncertain
0.0020
D;D;D;D;D
Polyphen
1.0
D;D;.;D;.
Vest4
0.93
MutPred
0.88
Loss of MoRF binding (P = 5e-04);Loss of MoRF binding (P = 5e-04);.;.;.;
MVP
0.56
MPC
0.40
ClinPred
0.99
D
GERP RS
4.9
Varity_R
0.92
gMVP
0.91

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: rs779901301; hg19: chr17-17425702; API