rs572671874

Variant names:

• chr17-17512554-C-T
• rs572671874
• NM_148172.3:c.421G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-17512554-C-T
• chr17-17512554-C-A
• chr17-17512554-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_148172.3(PEMT):​c.421G>A​(p.Val141Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000218 in 1,608,482 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000019 (0 hom.)
• Consequence: PEMT NM_148172.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.58
• Publications: 2 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.859

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.421G>A	p.Val141Met	missense	Exon 4 of 7	NP_680477.1	Q9UBM1-2
	PEMT	NM_001267552.2		c.421G>A	p.Val141Met	missense	Exon 4 of 8	NP_001254481.1	Q9UBM1-3
	PEMT	NM_001267551.2		c.355G>A	p.Val119Met	missense	Exon 4 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.421G>A	p.Val141Met	missense	Exon 4 of 7	ENSP00000255389.5	Q9UBM1-2
	PEMT	ENST00000395782.5	TSL:1	c.310G>A	p.Val104Met	missense	Exon 4 of 7	ENSP00000379128.1	Q9UBM1-1
	PEMT	ENST00000395783.5	TSL:1	c.310G>A	p.Val104Met	missense	Exon 4 of 7	ENSP00000379129.1	Q9UBM1-1

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152222 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000367 AC: 9 AN: 245440 AF XY: 0.0000150

Gnomad AFR exome AF: 0.0000632

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000111

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000540

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000192 AC: 28 AN: 1456260 Hom.: 0 Cov.: 31 AF XY: 0.0000152 AC XY: 11 AN XY: 724300

African (AFR) AF: 0.0000300 AC: 1 AN: 33324

American (AMR) AF: 0.0000226 AC: 1 AN: 44270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26018

East Asian (EAS) AF: 0.0000254 AC: 1 AN: 39356

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85382

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52576

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5758

European-Non Finnish (NFE) AF: 0.0000189 AC: 21 AN: 1109410

Other (OTH) AF: 0.0000332 AC: 2 AN: 60166

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152222 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74370

African (AFR) AF: 0.00 AC: 0 AN: 41456

American (AMR) AF: 0.00 AC: 0 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10632

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68030

Other (OTH) AF: 0.000478 AC: 1 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000264

ExAC AF: 0.0000577 AC: 7

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	Uncertain	0.51
BayesDel_addAF	Benign	-0.023	T
BayesDel_noAF	Uncertain	-0.040
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.56	D
Eigen	Pathogenic	0.77
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.029	D
MetaRNN	Pathogenic	0.86	D
MetaSVM	Uncertain	-0.0059	T
MutationAssessor	Pathogenic	3.6	H
PhyloP100		6.6
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-3.0	D
REVEL	Uncertain	0.47
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.87
MutPred		0.74		Gain of helix (P = 0.0696)
MVP		0.50
MPC		0.45
ClinPred		0.99	D
GERP RS		5.0
Varity_R		0.89
gMVP		0.88
Mutation Taster		=56/44	polymorphism

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: rs572671874; hg19: chr17-17415868; COSMIC: COSV55132323; COSMIC: COSV55132323;