Variant 17-76468832-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_001088.3(AANAT):c.86G>A(p.Arg29His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000227 in 1,613,450 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0013 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

AANAT
NM_001088.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 9.31

Variant links:

Genes affected

AANAT (HGNC:19): (aralkylamine N-acetyltransferase) The protein encoded by this gene belongs to the acetyltransferase superfamily. It is the penultimate enzyme in melatonin synthesis and controls the night/day rhythm in melatonin production in the vertebrate pineal gland. Melatonin is essential for the function of the circadian clock that influences activity and sleep. This enzyme is regulated by cAMP-dependent phosphorylation that promotes its interaction with 14-3-3 proteins and thus protects the enzyme against proteasomal degradation. This gene may contribute to numerous genetic diseases such as delayed sleep phase syndrome. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009]

AANAT 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=0.011256874).

BP6

Variant 17-76468832-G-A is Benign according to our data. Variant chr17-76468832-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 777222.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
AANAT	NM_001088.3 linkuse as main transcript	c.86G>A	p.Arg29His	missense_variant	2/4	ENST00000392492.8
AANAT	NM_001166579.2 linkuse as main transcript	c.221G>A	p.Arg74His	missense_variant	5/7
AANAT	NR_110548.2 linkuse as main transcript	n.286G>A		non_coding_transcript_exon_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AANAT	ENST00000392492.8 linkuse as main transcript	c.86G>A	p.Arg29His	missense_variant	2/4	1	NM_001088.3	P1	Q16613-1
AANAT	ENST00000250615.7 linkuse as main transcript	c.221G>A	p.Arg74His	missense_variant	5/7	1			Q16613-2
AANAT	ENST00000585649.1 linkuse as main transcript	c.200G>A	p.Arg67His	missense_variant	1/3	1
AANAT	ENST00000587798.1 linkuse as main transcript	c.86G>A	p.Arg29His	missense_variant, NMD_transcript_variant	2/4	5

Frequencies

GnomAD3 genomes

AF:

0.00124

AC:

189

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00444

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000316

AC:

AN:

249984

Hom.:

AF XY:

0.000266

AC XY:

AN XY:

135394

show subpopulations

Gnomad AFR exome

AF:

0.00464

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000120

AC:

175

AN:

1461208

Hom.:

Cov.:

AF XY:

0.000109

AC XY:

AN XY:

726938

show subpopulations

Gnomad4 AFR exome

AF:

0.00448

Gnomad4 AMR exome

AF:

0.000179

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:

0.00000270

Gnomad4 OTH exome

AF:

0.000215

GnomAD4 genome

AF:

0.00126

AC:

192

AN:

152242

Hom.:

Cov.:

AF XY:

0.00130

AC XY:

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.00450

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000278

Hom.:

Bravo

AF:

0.00141

ESP6500AA

AF:

0.00318

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000420

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Apr 24, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.13

CADD

Pathogenic

DANN

Pathogenic

1.0

Eigen

Pathogenic

0.77

Eigen_PC

Pathogenic

0.68

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.93

D;D;D

M_CAP

Uncertain

0.21

MetaRNN

Benign

0.011

T;T;T

MetaSVM

Uncertain

-0.18

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-1.5

N;N;.

REVEL

Uncertain

0.34

Sift

Uncertain

0.0010

D;D;.

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

.;D;.

Vest4

0.81

MVP

0.83

MPC

0.40

ClinPred

0.14

GERP RS

4.3

Varity_R

0.33

gMVP

0.66

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

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