NM_002686.4:c.202+159A>T

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002686.4(PNMT):​c.202+159A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PNMT	NM_002686.4	c.202+159A>T		intron_variant	Intron 1 of 2	ENST00000269582.3	NP_002677.1
PNMT	XM_011524909.3	c.-278A>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 3		XP_011523211.1
PNMT	XM_011524909.3	c.-278A>T		5_prime_UTR_variant	Exon 1 of 3		XP_011523211.1
PNMT	NR_073461.2	n.52+766A>T		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PNMT	ENST00000269582.3	c.202+159A>T		intron_variant	Intron 1 of 2	1	NM_002686.4	ENSP00000269582.2
PNMT	ENST00000394246.1	c.-93+766A>T		intron_variant	Intron 1 of 2	2		ENSP00000377791.1
PNMT	ENST00000581428.1	c.202+159A>T		intron_variant	Intron 1 of 1	2		ENSP00000464234.1

Frequencies

GnomAD3 genomes Cov.: 28

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

GnomAD4 genome Cov.: 28

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.8
DANN	Benign	0.76

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;