ENST00000394246.1:c.-93+16G>A

Variant names:

• chr17-39668086-G-A
• rs3764351
• ENST00000394246.1:c.-93+16G>A

Variant summary

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

The ENST00000394246.1(PNMT):​c.-93+16G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.55 (23938 hom., cov: 20)
  • Exomes 𝑓: 0.61 (7345 hom.)
• Consequence: PNMT ENST00000394246.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.697
• Publications: 34 publications found

Genes affected

PNMT (HGNC:9160): (phenylethanolamine N-methyltransferase) The product of this gene catalyzes the last step of the catecholamine biosynthesis pathway, which methylates norepinephrine to form epinephrine (adrenaline). The enzyme also has beta-carboline 2N-methyltransferase activity. This gene is thought to play a key step in regulating epinephrine production. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Nov 2012]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.68 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PNMT	NR_073461.2	n.52+16G>A		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PNMT	ENST00000394246.1	c.-93+16G>A		intron_variant	Intron 1 of 2	2		ENSP00000377791.1

Frequencies

GnomAD3 genomes AF: 0.549 AC: 80621 AN: 146814 Hom.: 23935 Cov.: 20

Gnomad AFR AF: 0.331

Gnomad AMI AF: 0.740

Gnomad AMR AF: 0.534

Gnomad ASJ AF: 0.670

Gnomad EAS AF: 0.425

Gnomad SAS AF: 0.700

Gnomad FIN AF: 0.692

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.650

Gnomad OTH AF: 0.559

GnomAD4 exome AF: 0.610 AC: 21164 AN: 34710 Hom.: 7345 Cov.: 0 AF XY: 0.618 AC XY: 10692 AN XY: 17314

African (AFR) AF: 0.279 AC: 419 AN: 1500

American (AMR) AF: 0.522 AC: 449 AN: 860

Ashkenazi Jewish (ASJ) AF: 0.669 AC: 1018 AN: 1522

East Asian (EAS) AF: 0.456 AC: 1234 AN: 2708

South Asian (SAS) AF: 0.695 AC: 332 AN: 478

European-Finnish (FIN) AF: 0.646 AC: 1188 AN: 1838

Middle Eastern (MID) AF: 0.621 AC: 133 AN: 214

European-Non Finnish (NFE) AF: 0.645 AC: 14933 AN: 23158

Other (OTH) AF: 0.600 AC: 1458 AN: 2432

GnomAD4 genome AF: 0.549 AC: 80652 AN: 146924 Hom.: 23938 Cov.: 20 AF XY: 0.549 AC XY: 39255 AN XY: 71474

African (AFR) AF: 0.331 AC: 13143 AN: 39718

American (AMR) AF: 0.534 AC: 7917 AN: 14820

Ashkenazi Jewish (ASJ) AF: 0.670 AC: 2293 AN: 3424

East Asian (EAS) AF: 0.425 AC: 2028 AN: 4774

South Asian (SAS) AF: 0.700 AC: 3158 AN: 4512

European-Finnish (FIN) AF: 0.692 AC: 6929 AN: 10008

Middle Eastern (MID) AF: 0.594 AC: 170 AN: 286

European-Non Finnish (NFE) AF: 0.650 AC: 43216 AN: 66456

Other (OTH) AF: 0.560 AC: 1141 AN: 2038

Alfa AF: 0.613 Hom.: 48112

Bravo AF: 0.525

Asia WGS AF: 0.590 AC: 2046 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.3
DANN	Benign	0.73
PhyloP100		-0.70
PromoterAI		0.043	Neutral
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: rs3764351; hg19: chr17-37824339;