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17-76469712-T-C

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_001088.3(AANAT):c.366T>C(p.His122=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00112 in 1,538,028 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0010 ( 1 hom., cov: 32)
Exomes 𝑓: 0.0011 ( 0 hom. )

Consequence

AANAT
NM_001088.3 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.320
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 Likely_benign. Variant got -5 ACMG points.

PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
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=-0.69).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 17-76469712-T-C is Benign according to our data. Variant chr17-76469712-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 790430.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=0.32 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
AANATNM_001088.3 linkuse as main transcriptc.366T>C p.His122= synonymous_variant 4/4 ENST00000392492.8
AANATNM_001166579.2 linkuse as main transcriptc.501T>C p.His167= synonymous_variant 7/7
AANATNR_110548.2 linkuse as main transcriptn.622T>C 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.366T>C p.His122= synonymous_variant 4/41 NM_001088.3 P1Q16613-1
AANATENST00000250615.7 linkuse as main transcriptc.501T>C p.His167= synonymous_variant 7/71 Q16613-2
AANATENST00000587798.1 linkuse as main transcriptc.*143T>C 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:
0.00102
AC:
156
AN:
152212
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000265
Gnomad AMI
AF:
0.0307
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000282
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00163
Gnomad OTH
AF:
0.00144
GnomAD3 exomes
AF:
0.000548
AC:
95
AN:
173486
Hom.:
0
AF XY:
0.000552
AC XY:
52
AN XY:
94232
show subpopulations
Gnomad AFR exome
AF:
0.000250
Gnomad AMR exome
AF:
0.000155
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.000277
Gnomad NFE exome
AF:
0.00108
Gnomad OTH exome
AF:
0.000230
GnomAD4 exome
AF:
0.00114
AC:
1574
AN:
1385698
Hom.:
0
Cov.:
31
AF XY:
0.00112
AC XY:
765
AN XY:
680372
show subpopulations
Gnomad4 AFR exome
AF:
0.000157
Gnomad4 AMR exome
AF:
0.000220
Gnomad4 ASJ exome
AF:
0.0000450
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000265
Gnomad4 FIN exome
AF:
0.000684
Gnomad4 NFE exome
AF:
0.00139
Gnomad4 OTH exome
AF:
0.000543
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00102
AC:
156
AN:
152330
Hom.:
1
Cov.:
32
AF XY:
0.00110
AC XY:
82
AN XY:
74484
show subpopulations
Gnomad4 AFR
AF:
0.000265
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000282
Gnomad4 NFE
AF:
0.00163
Gnomad4 OTH
AF:
0.00142
Alfa
AF:
0.000804
Hom.:
0
Bravo
AF:
0.00103

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 testingInvitaeMay 24, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.69
Cadd
Benign
2.6
Dann
Benign
0.51

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.

Other links and lift over

dbSNP: rs140194920; hg19: chr17-74465794; API