Variant chr17-39670018-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002686.4(PNMT):c.478C>T(p.His160Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000000688 in 1,452,790 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

PNMT
NM_002686.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.05

Variant links:

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]

PNMT links:

PNMT (HGNC:):

PNMT links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PNMT	NM_002686.4 linkuse as main transcript	c.478C>T	p.His160Tyr	missense_variant	3/3	ENST00000269582.3	NP_002677.1	P11086
PNMT	XM_011524909.3 linkuse as main transcript	c.184C>T	p.His62Tyr	missense_variant	3/3		XP_011523211.1	A8MT87
PNMT	NR_073461.2 linkuse as main transcript	n.328C>T		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PNMT	ENST00000269582.3 linkuse as main transcript	c.478C>T	p.His160Tyr	missense_variant	3/3	1	NM_002686.4	ENSP00000269582.2	P11086
PNMT	ENST00000394246.1 linkuse as main transcript	c.184C>T	p.His62Tyr	missense_variant	3/3	2		ENSP00000377791.1	A8MT87
PNMT	ENST00000581428.1 linkuse as main transcript	c.*178C>T		3_prime_UTR_variant	2/2	2		ENSP00000464234.1	J3QRI3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.88e-7

AC:

AN:

1452790

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

723164

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 06, 2021

The c.478C>T (p.H160Y) alteration is located in exon 3 (coding exon 3) of the PNMT gene. This alteration results from a C to T substitution at nucleotide position 478, causing the histidine (H) at amino acid position 160 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.35

BayesDel_addAF

Benign

-0.075

BayesDel_noAF

Benign

-0.35

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.19

.;T

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.88

D;D

M_CAP

Benign

0.017

MetaRNN

Uncertain

0.71

D;D

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.7

.;M

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-2.0

N;N

REVEL

Benign

0.24

Sift

Benign

0.045

D;T

Sift4G

Benign

0.066

T;T

Polyphen

1.0

.;D

Vest4

0.58

MutPred

0.61

.;Gain of phosphorylation at H160 (P = 0.0068);

MVP

0.35

MPC

0.94

ClinPred

0.96

GERP RS

4.8

Varity_R

0.76

gMVP

0.63

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over