Variant chr17-76469730-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001088.3(AANAT):c.384C>T(p.Arg128=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000497 in 1,555,210 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00032 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00052 ( 9 hom. )

Consequence

AANAT
NM_001088.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0910

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP6

Variant 17-76469730-C-T is Benign according to our data. Variant chr17-76469730-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2648316.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.091 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
AANAT	NM_001088.3 linkuse as main transcript	c.384C>T	p.Arg128=	synonymous_variant	4/4	ENST00000392492.8
AANAT	NM_001166579.2 linkuse as main transcript	c.519C>T	p.Arg173=	synonymous_variant	7/7
AANAT	NR_110548.2 linkuse as main transcript	n.640C>T		non_coding_transcript_exon_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AANAT	ENST00000392492.8 linkuse as main transcript	c.384C>T	p.Arg128=	synonymous_variant	4/4	1	NM_001088.3	P1	Q16613-1
AANAT	ENST00000250615.7 linkuse as main transcript	c.519C>T	p.Arg173=	synonymous_variant	7/7	1			Q16613-2
AANAT	ENST00000587798.1 linkuse as main transcript	c.*161C>T		3_prime_UTR_variant, NMD_transcript_variant	4/4	5
AANAT	ENST00000585649.1 linkuse as main transcript			downstream_gene_variant		1

Frequencies

GnomAD3 genomes

AF:

0.000315

AC:

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00641

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00105

AC:

189

AN:

179864

Hom.:

AF XY:

0.00137

AC XY:

135

AN XY:

98286

show subpopulations

Gnomad AFR exome

AF:

0.0000882

Gnomad AMR exome

AF:

0.000111

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000135

Gnomad SAS exome

AF:

0.00729

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000257

Gnomad OTH exome

AF:

0.000436

GnomAD4 exome

AF:

0.000517

AC:

725

AN:

1402860

Hom.:

Cov.:

AF XY:

0.000741

AC XY:

512

AN XY:

691348

show subpopulations

Gnomad4 AFR exome

AF:

0.0000620

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000263

Gnomad4 SAS exome

AF:

0.00655

Gnomad4 FIN exome

AF:

0.0000208

Gnomad4 NFE exome

AF:

0.000146

Gnomad4 OTH exome

AF:

0.000658

GnomAD4 genome

AF:

0.000315

AC:

AN:

152350

Hom.:

Cov.:

AF XY:

0.000497

AC XY:

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00641

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000154

Hom.:

Bravo

AF:

0.000147

Asia WGS

AF:

0.00173

AC:

AN:

3478

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

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

AANAT: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

5.4

DANN

Benign

0.84

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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