chr17-17522319-C-T

Variant names:

• chr17-17522319-C-T
• NM_148172.3:c.281G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_148172.3(PEMT):​c.281G>A​(p.Ser94Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 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)
• Consequence: PEMT NM_148172.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.36
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35459346).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_148172.3. 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
	PEMT	NM_148172.3	MANE Select	c.281G>A	p.Ser94Asn	missense	Exon 3 of 7	NP_680477.1	Q9UBM1-2
	PEMT	NM_001267552.2		c.281G>A	p.Ser94Asn	missense	Exon 3 of 8	NP_001254481.1	Q9UBM1-3
	PEMT	NM_001267551.2		c.215G>A	p.Ser72Asn	missense	Exon 3 of 7	NP_001254480.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PEMT	ENST00000255389.10	TSL:1 MANE Select	c.281G>A	p.Ser94Asn	missense	Exon 3 of 7	ENSP00000255389.5	Q9UBM1-2
	PEMT	ENST00000395782.5	TSL:1	c.170G>A	p.Ser57Asn	missense	Exon 3 of 7	ENSP00000379128.1	Q9UBM1-1
	PEMT	ENST00000395783.5	TSL:1	c.170G>A	p.Ser57Asn	missense	Exon 3 of 7	ENSP00000379129.1	Q9UBM1-1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

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	Pathogenic	0.75
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	T
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.074
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L
PhyloP100		4.4
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.11
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.28	B
Vest4		0.24
MutPred		0.70		Loss of stability (P = 0.1899)
MVP		0.33
MPC		0.10
ClinPred		0.54	D
GERP RS		4.9
Varity_R		0.33
gMVP		0.78

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

hg19: chr17-17425633;