rs141006262

Variant names:

Variant summary

Our verdict is Benign. The variant received -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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R29C) has been classified as Uncertain significance.

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

Publications

3 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 777222.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001088.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AANAT	NM_001088.3	MANE Select	c.86G>A	p.Arg29His	missense	Exon 2 of 4	NP_001079.1	F1T0I5
AANAT	NM_001166579.2		c.221G>A	p.Arg74His	missense	Exon 5 of 7	NP_001160051.1	Q16613-2
AANAT	NR_110548.2		n.286G>A		non_coding_transcript_exon	Exon 2 of 4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AANAT	ENST00000392492.8	TSL:1 MANE Select	c.86G>A	p.Arg29His	missense	Exon 2 of 4	ENSP00000376282.2	Q16613-1
AANAT	ENST00000250615.7	TSL:1	c.221G>A	p.Arg74His	missense	Exon 5 of 7	ENSP00000250615.2	Q16613-2
AANAT	ENST00000585649.1	TSL:1	c.200G>A	p.Arg67His	missense	Exon 1 of 3	ENSP00000468717.1	K7ESH7

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

GnomAD2 exomes

AF:

0.000316

AC:

AN:

249984

AF XY:

0.000266

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 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

African (AFR)

AF:

0.00448

AC:

150

AN:

33480

American (AMR)

AF:

0.000179

AC:

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52798

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000270

AC:

AN:

1111984

Other (OTH)

AF:

0.000215

AC:

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00126

AC:

192

AN:

152242

Hom.:

Cov.:

AF XY:

0.00130

AC XY:

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.00450

AC:

187

AN:

41534

American (AMR)

AF:

0.000327

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68002

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000360

Hom.:

Bravo

AF:

0.00141

ESP6500AA

AF:

0.00318

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000420

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.13

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.26

Eigen

Pathogenic

0.77

Eigen_PC

Pathogenic

0.68

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.93

M_CAP

Uncertain

0.21

MetaRNN

Benign

0.011

MetaSVM

Uncertain

-0.18

MutationAssessor

Uncertain

2.9

PhyloP100

9.3

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-1.5

REVEL

Uncertain

0.34

Sift

Uncertain

0.0010

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.81

MVP

0.83

MPC

0.40

ClinPred

0.14

GERP RS

4.3

PromoterAI

0.0046

Neutral

(source)

Varity_R

0.33

gMVP

0.66

Mutation Taster

=63/37

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over