17-17522319-C-T

Position:

• chr17-17522319-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 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. 12/21 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)
• Consequence: PEMT NM_148172.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.36

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 Uncertain_significance. Variant got 1 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PEMT	NM_148172.3	c.281G>A	p.Ser94Asn	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.281G>A	p.Ser94Asn	missense_variant	3/7	1	NM_148172.3	ENSP00000255389.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 21, 2024

The c.170G>A (p.S57N) alteration is located in exon 3 (coding exon 2) of the PEMT gene. This alteration results from a G to A substitution at nucleotide position 170, causing the serine (S) at amino acid position 57 to be replaced by an asparagine (N). 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	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;T;.;.;.
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.074
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Uncertain	0.94	.;D;D;D;D
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.35	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L;L;.;.;.
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.9	N;N;N;N;N
REVEL	Benign	0.11
Sift	Uncertain	0.0010	D;D;D;D;D
Sift4G	Uncertain	0.0020	D;D;D;D;D
Polyphen		0.28	B;B;.;P;.
Vest4		0.24
MutPred		0.70		Loss of stability (P = 0.1899);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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-17425633;