Variant 17-17577005-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_148172.3(PEMT):c.119G>T(p.Arg40Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,638 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

PEMT
NM_148172.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.103

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]

PEMT links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.22274396).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PEMT	NM_148172.3 link	c.119G>T	p.Arg40Leu	missense_variant	2/7	ENST00000255389.10	NP_680477.1	Q9UBM1-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PEMT	ENST00000255389.10 link	c.119G>T	p.Arg40Leu	missense_variant	2/7	1	NM_148172.3	ENSP00000255389.5		Q9UBM1-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461638

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727124

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:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

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 submitter

clinical testing

Ambry Genetics

Sep 26, 2022

The c.8G>T (p.R3L) alteration is located in exon 2 (coding exon 1) of the PEMT gene. This alteration results from a G to T substitution at nucleotide position 8, causing the arginine (R) at amino acid position 3 to be replaced by a leucine (L). 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

0.091

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.11

T;T;.;.;.

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.75

FATHMM_MKL

Benign

0.037

LIST_S2

Benign

0.72

.;T;T;T;T

M_CAP

Benign

0.010

MetaRNN

Benign

0.22

T;T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.7

L;L;.;.;.

PrimateAI

Benign

0.23

PROVEAN

Benign

-1.8

N;N;N;N;N

REVEL

Benign

0.080

Sift

Benign

0.28

T;T;T;T;T

Sift4G

Benign

0.28

T;T;T;T;T

Polyphen

0.037

B;B;.;B;.

Vest4

0.35

MutPred

0.45

Gain of sheet (P = 0.0125);Gain of sheet (P = 0.0125);.;.;.;

MVP

0.61

MPC

0.099

ClinPred

0.11

GERP RS

0.77

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.063

gMVP

0.33

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over