chr17-17522317-C-T

Variant names:

• chr17-17522317-C-T
• rs897453
• NM_148172.3:c.283G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_148172.3(PEMT):​c.283G>A​(p.Val95Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 1,612,294 control chromosomes in the GnomAD database, including 147,564 homozygotes. 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: 𝑓 0.33 (9812 hom., cov: 31)
  • Exomes 𝑓: 0.42 (137752 hom.)
• Consequence: PEMT NM_148172.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0210
• Publications: 47 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=3.1906366E-4).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PEMT	NM_148172.3	c.283G>A	p.Val95Ile	missense_variant	Exon 3 of 7	ENST00000255389.10	NP_680477.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PEMT	ENST00000255389.10	c.283G>A	p.Val95Ile	missense_variant	Exon 3 of 7	1	NM_148172.3	ENSP00000255389.5

Frequencies

GnomAD3 genomes AF: 0.327 AC: 49633 AN: 151926 Hom.: 9816 Cov.: 31

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.492

Gnomad AMR AF: 0.321

Gnomad ASJ AF: 0.358

Gnomad EAS AF: 0.0981

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.400

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.461

Gnomad OTH AF: 0.338

GnomAD2 exomes AF: 0.340 AC: 85115 AN: 250372 AF XY: 0.345

Gnomad AFR exome AF: 0.112

Gnomad AMR exome AF: 0.237

Gnomad ASJ exome AF: 0.372

Gnomad EAS exome AF: 0.0940

Gnomad FIN exome AF: 0.412

Gnomad NFE exome AF: 0.459

Gnomad OTH exome AF: 0.399

GnomAD4 exome AF: 0.422 AC: 615538 AN: 1460250 Hom.: 137752 Cov.: 36 AF XY: 0.416 AC XY: 302262 AN XY: 726450

African (AFR) AF: 0.111 AC: 3699 AN: 33474

American (AMR) AF: 0.249 AC: 11137 AN: 44674

Ashkenazi Jewish (ASJ) AF: 0.368 AC: 9622 AN: 26112

East Asian (EAS) AF: 0.141 AC: 5593 AN: 39688

South Asian (SAS) AF: 0.212 AC: 18296 AN: 86210

European-Finnish (FIN) AF: 0.414 AC: 22100 AN: 53364

Middle Eastern (MID) AF: 0.341 AC: 1963 AN: 5762

European-Non Finnish (NFE) AF: 0.468 AC: 519596 AN: 1110616

Other (OTH) AF: 0.390 AC: 23532 AN: 60350

GnomAD4 genome AF: 0.326 AC: 49623 AN: 152044 Hom.: 9812 Cov.: 31 AF XY: 0.321 AC XY: 23814 AN XY: 74276

African (AFR) AF: 0.124 AC: 5166 AN: 41506

American (AMR) AF: 0.321 AC: 4905 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.358 AC: 1242 AN: 3468

East Asian (EAS) AF: 0.0978 AC: 504 AN: 5156

South Asian (SAS) AF: 0.201 AC: 968 AN: 4818

European-Finnish (FIN) AF: 0.400 AC: 4219 AN: 10542

Middle Eastern (MID) AF: 0.418 AC: 123 AN: 294

European-Non Finnish (NFE) AF: 0.461 AC: 31336 AN: 67938

Other (OTH) AF: 0.336 AC: 711 AN: 2116

Alfa AF: 0.400 Hom.: 39278

Bravo AF: 0.313

TwinsUK AF: 0.476 AC: 1766

ALSPAC AF: 0.488 AC: 1881

ESP6500AA AF: 0.130 AC: 574

ESP6500EA AF: 0.451 AC: 3877

ExAC AF: 0.342 AC: 41557

Asia WGS AF: 0.174 AC: 604 AN: 3478

EpiCase AF: 0.443

EpiControl AF: 0.454

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.80	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.70
DANN	Benign	0.75
DEOGEN2	Benign	0.060	T;T;.;.;.
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0098	N
LIST_S2	Benign	0.77	.;T;T;T;T
MetaRNN	Benign	0.00032	T;T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-0.36	N;N;.;.;.
PhyloP100		-0.021
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.27	N;N;N;N;N
REVEL	Benign	0.0090
Sift	Benign	0.67	T;T;T;T;T
Sift4G	Benign	0.74	T;T;T;T;T
Polyphen		0.0010	B;B;.;B;.
Vest4		0.024
MPC		0.065
ClinPred		0.00055	T
GERP RS		-5.1
Varity_R		0.017
gMVP		0.27
Mutation Taster		=100/0	polymorphism (auto)

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

dbSNP: rs897453; hg19: chr17-17425631; COSMIC: COSV55131208; COSMIC: COSV55131208;