17-17583205-C-G

Variant names:

• chr17-17583205-C-G
• rs12325817
• NM_148172.3:c.97-6178G>C

Variant summary

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

The NM_148172.3(PEMT):​c.97-6178G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 151,868 control chromosomes in the GnomAD database, including 10,028 homozygotes. In-silico tool predicts 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 (10028 hom., cov: 31)
• Consequence: PEMT NM_148172.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.717
• Publications: 68 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]

EEF1A1P43 (HGNC:3193):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PEMT	NM_148172.3	c.97-6178G>C		intron_variant	Intron 1 of 6	ENST00000255389.10	NP_680477.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PEMT	ENST00000255389.10	c.97-6178G>C		intron_variant	Intron 1 of 6	1	NM_148172.3	ENSP00000255389.5

Frequencies

GnomAD3 genomes AF: 0.335 AC: 50850 AN: 151750 Hom.: 10026 Cov.: 31

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.416

Gnomad AMR AF: 0.391

Gnomad ASJ AF: 0.402

Gnomad EAS AF: 0.175

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.390

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.453

Gnomad OTH AF: 0.350

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.335 AC: 50862 AN: 151868 Hom.: 10028 Cov.: 31 AF XY: 0.330 AC XY: 24462 AN XY: 74190

African (AFR) AF: 0.131 AC: 5420 AN: 41414

American (AMR) AF: 0.391 AC: 5973 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.402 AC: 1395 AN: 3468

East Asian (EAS) AF: 0.175 AC: 903 AN: 5156

South Asian (SAS) AF: 0.216 AC: 1039 AN: 4810

European-Finnish (FIN) AF: 0.390 AC: 4106 AN: 10520

Middle Eastern (MID) AF: 0.463 AC: 136 AN: 294

European-Non Finnish (NFE) AF: 0.453 AC: 30779 AN: 67930

Other (OTH) AF: 0.348 AC: 732 AN: 2104

Alfa AF: 0.243 Hom.: 617

Bravo AF: 0.327

Asia WGS AF: 0.218 AC: 759 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.59
DANN	Benign	0.60
PhyloP100		-0.72
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs12325817; hg19: chr17-17486519;