17-17522317-C-A

Position:

• chr17-17522317-C-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0210

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]

ACMG classification

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
PEMT	NM_148172.3	c.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
PEMT	ENST00000255389.10	c.283G>T	p.Val95Phe	missense_variant	3/7	1	NM_148172.3	ENSP00000255389

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

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

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

Other links and lift over

dbSNP: rs897453; hg19: chr17-17425631;