rs200173

Positions:

• chr17-39668836-A-G
• chr17-39668836-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002686.4(PNMT):​c.202+159A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.99 in 152,132 control chromosomes in the GnomAD database, including 74,627 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 0.99 (74627 hom., cov: 28)
• Consequence: PNMT NM_002686.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.675

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.989 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PNMT	NM_002686.4	c.202+159A>G		intron_variant		ENST00000269582.3
PNMT	XM_011524909.3	c.-278A>G		5_prime_UTR_variant	1/3
PNMT	NR_073461.2	n.52+766A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PNMT	ENST00000269582.3	c.202+159A>G		intron_variant		1	NM_002686.4	P1
PNMT	ENST00000394246.1	c.-93+766A>G		intron_variant		2
PNMT	ENST00000581428.1	c.202+159A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.990 AC: 150561 AN: 152014 Hom.: 74568 Cov.: 28

Gnomad AFR AF: 0.997

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.986

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.999

Gnomad FIN AF: 0.995

Gnomad MID AF: 0.990

Gnomad NFE AF: 0.985

Gnomad OTH AF: 0.987

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

GnomAD4 genome AF: 0.990 AC: 150679 AN: 152132 Hom.: 74627 Cov.: 28 AF XY: 0.991 AC XY: 73692 AN XY: 74364

Gnomad4 AFR AF: 0.997

Gnomad4 AMR AF: 0.986

Gnomad4 ASJ AF: 1.00

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.999

Gnomad4 FIN AF: 0.995

Gnomad4 NFE AF: 0.985

Gnomad4 OTH AF: 0.987

Alfa AF: 0.987 Hom.: 9359

Bravo AF: 0.990

Asia WGS AF: 0.998 AC: 3472 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.0
DANN	Benign	0.67

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

Publications

LitVar

Other links and lift over

dbSNP: rs200173; hg19: chr17-37825089;