rs200173

Variant names:

• chr17-39668836-A-G
• rs200173
• NM_002686.4:c.202+159A>G

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.989 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002686.4. 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
	PNMT	NM_002686.4	MANE Select	c.202+159A>G		intron	N/A	NP_002677.1	P11086
	PNMT	NR_073461.2		n.52+766A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PNMT	ENST00000269582.3	TSL:1 MANE Select	c.202+159A>G		intron	N/A	ENSP00000269582.2	P11086
	PNMT	ENST00000394246.1	TSL:2	c.-93+766A>G		intron	N/A	ENSP00000377791.1	A8MT87
	PNMT	ENST00000581428.1	TSL:2	c.202+159A>G		intron	N/A	ENSP00000464234.1	J3QRI3

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

African (AFR) AF: 0.997 AC: 41375 AN: 41496

American (AMR) AF: 0.986 AC: 15070 AN: 15284

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3471 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5152 AN: 5152

South Asian (SAS) AF: 0.999 AC: 4802 AN: 4806

European-Finnish (FIN) AF: 0.995 AC: 10527 AN: 10584

Middle Eastern (MID) AF: 0.990 AC: 289 AN: 292

European-Non Finnish (NFE) AF: 0.985 AC: 67000 AN: 68026

Other (OTH) AF: 0.987 AC: 2083 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.0
DANN	Benign	0.67
PhyloP100		0.68
PromoterAI		0.011	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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: rs200173; hg19: chr17-37825089;