Variant chr17-39670063-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_002686.4(PNMT):c.523G>A(p.Ala175Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00479 in 1,607,906 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0037 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0049 ( 20 hom. )

Consequence

PNMT
NM_002686.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.41

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012893349).

BP6

Variant 17-39670063-G-A is Benign according to our data. Variant chr17-39670063-G-A is described in ClinVar as [Benign]. Clinvar id is 770446.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PNMT	NM_002686.4 linkuse as main transcript	c.523G>A	p.Ala175Thr	missense_variant	3/3	ENST00000269582.3	NP_002677.1	P11086
PNMT	XM_011524909.3 linkuse as main transcript	c.229G>A	p.Ala77Thr	missense_variant	3/3		XP_011523211.1	A8MT87
PNMT	NR_073461.2 linkuse as main transcript	n.373G>A		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.523G>A	p.Ala175Thr	missense_variant	3/3	1	NM_002686.4	ENSP00000269582.2	P11086
PNMT	ENST00000394246.1 linkuse as main transcript	c.229G>A	p.Ala77Thr	missense_variant	3/3	2		ENSP00000377791.1	A8MT87
PNMT	ENST00000581428.1 linkuse as main transcript	c.*223G>A		3_prime_UTR_variant	2/2	2		ENSP00000464234.1	J3QRI3

Frequencies

GnomAD3 genomes

AF:

0.00375

AC:

570

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00113

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.00131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.0125

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00519

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00359

AC:

884

AN:

246278

Hom.:

AF XY:

0.00375

AC XY:

502

AN XY:

133822

show subpopulations

Gnomad AFR exome

AF:

0.000620

Gnomad AMR exome

AF:

0.00150

Gnomad ASJ exome

AF:

0.0000995

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00154

Gnomad FIN exome

AF:

0.0109

Gnomad NFE exome

AF:

0.00489

Gnomad OTH exome

AF:

0.00509

GnomAD4 exome

AF:

0.00490

AC:

7137

AN:

1455630

Hom.:

Cov.:

AF XY:

0.00485

AC XY:

3514

AN XY:

724512

show subpopulations

Gnomad4 AFR exome

AF:

0.000717

Gnomad4 AMR exome

AF:

0.00145

Gnomad4 ASJ exome

AF:

0.0000766

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00182

Gnomad4 FIN exome

AF:

0.0113

Gnomad4 NFE exome

AF:

0.00549

Gnomad4 OTH exome

AF:

0.00409

GnomAD4 genome

AF:

0.00374

AC:

570

AN:

152276

Hom.:

Cov.:

AF XY:

0.00402

AC XY:

299

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.00113

Gnomad4 AMR

AF:

0.00131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.0125

Gnomad4 NFE

AF:

0.00519

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00434

Hom.:

Bravo

AF:

0.00281

TwinsUK

AF:

0.00620

AC:

ALSPAC

AF:

0.00623

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00442

AC:

ExAC

AF:

0.00354

AC:

430

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00414

EpiControl

AF:

0.00445

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 20, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.53

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.32

.;T

Eigen

Benign

-0.12

Eigen_PC

Benign

-0.031

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.69

T;T

MetaRNN

Benign

0.013

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.4

.;M

PrimateAI

Uncertain

0.55

PROVEAN

Uncertain

-2.9

D;D

REVEL

Benign

0.076

Sift

Uncertain

0.022

D;D

Sift4G

Benign

0.099

T;T

Polyphen

0.042

.;B

Vest4

0.094

MVP

0.20

MPC

0.26

ClinPred

0.019

GERP RS

3.7

Varity_R

0.90

gMVP

0.65

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over