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GeneBe

17-76469730-C-T

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

2

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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.64).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.091 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAdExome at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
AANATNM_001088.3 linkuse as main transcriptc.384C>T p.Arg128= synonymous_variant 4/4 ENST00000392492.8
AANATNM_001166579.2 linkuse as main transcriptc.519C>T p.Arg173= synonymous_variant 7/7
AANATNR_110548.2 linkuse as main transcriptn.640C>T non_coding_transcript_exon_variant 4/4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
AANATENST00000392492.8 linkuse as main transcriptc.384C>T p.Arg128= synonymous_variant 4/41 NM_001088.3 P1Q16613-1
AANATENST00000250615.7 linkuse as main transcriptc.519C>T p.Arg173= synonymous_variant 7/71 Q16613-2
AANATENST00000587798.1 linkuse as main transcriptc.*161C>T 3_prime_UTR_variant, NMD_transcript_variant 4/45
AANATENST00000585649.1 linkuse as main transcript downstream_gene_variant 1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000315
AC:
48
AN:
152232
Hom.:
1
Cov.:
33
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.:
2
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.:
9
Cov.:
31
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
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000315
AC:
48
AN:
152350
Hom.:
1
Cov.:
33
AF XY:
0.000497
AC XY:
37
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.:
0
Bravo
AF:
0.000147
Asia WGS
AF:
0.00173
AC:
6
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 submitterclinical testingCeGaT Center for Human Genetics TuebingenMar 01, 2023AANAT: 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.

Other links and lift over

dbSNP: rs200468284; hg19: chr17-74465812; COSMIC: COSV51686118; COSMIC: COSV51686118; API