rs3764351

Positions:

• chr17-39668086-G-A

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
PNMT	NR_073461.2	n.52+16G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PNMT	ENST00000394246.1	c.-93+16G>A		intron_variant		2		ENSP00000377791

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

Gnomad4 AFR exome AF: 0.279

Gnomad4 AMR exome AF: 0.522

Gnomad4 ASJ exome AF: 0.669

Gnomad4 EAS exome AF: 0.456

Gnomad4 SAS exome AF: 0.695

Gnomad4 FIN exome AF: 0.646

Gnomad4 NFE exome AF: 0.645

Gnomad4 OTH exome AF: 0.600

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

Gnomad4 AFR AF: 0.331

Gnomad4 AMR AF: 0.534

Gnomad4 ASJ AF: 0.670

Gnomad4 EAS AF: 0.425

Gnomad4 SAS AF: 0.700

Gnomad4 FIN AF: 0.692

Gnomad4 NFE AF: 0.650

Gnomad4 OTH AF: 0.560

Alfa AF: 0.635 Hom.: 35985

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3764351; hg19: chr17-37824339;