rs140194920

Variant names:

• chr17-76469712-T-C
• rs140194920
• NM_001088.3:c.366T>C

Your query was ambiguous. Multiple possible variants found:

• chr17-76469712-T-C
• chr17-76469712-T-G

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_001088.3(AANAT):​c.366T>C​(p.His122His) 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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.320
• Publications: 1 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: 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: Synonymous conserved (PhyloP=0.32 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AANAT	NM_001088.3	c.366T>C	p.His122His	synonymous_variant	Exon 4 of 4	ENST00000392492.8	NP_001079.1
AANAT	NM_001166579.2	c.501T>C	p.His167His	synonymous_variant	Exon 7 of 7		NP_001160051.1
AANAT	NR_110548.2	n.622T>C		non_coding_transcript_exon_variant	Exon 4 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AANAT	ENST00000392492.8	c.366T>C	p.His122His	synonymous_variant	Exon 4 of 4	1	NM_001088.3	ENSP00000376282.2

Frequencies

GnomAD3 genomes AF: 0.00102 AC: 156 AN: 152212 Hom.: 1 Cov.: 32

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

GnomAD2 exomes AF: 0.000548 AC: 95 AN: 173486 AF XY: 0.000552

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 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

African (AFR) AF: 0.000157 AC: 5 AN: 31854

American (AMR) AF: 0.000220 AC: 8 AN: 36310

Ashkenazi Jewish (ASJ) AF: 0.0000450 AC: 1 AN: 22198

East Asian (EAS) AF: 0.00 AC: 0 AN: 38092

South Asian (SAS) AF: 0.0000265 AC: 2 AN: 75528

European-Finnish (FIN) AF: 0.000684 AC: 32 AN: 46794

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5112

European-Non Finnish (NFE) AF: 0.00139 AC: 1495 AN: 1072718

Other (OTH) AF: 0.000543 AC: 31 AN: 57092

GnomAD4 genome AF: 0.00102 AC: 156 AN: 152330 Hom.: 1 Cov.: 32 AF XY: 0.00110 AC XY: 82 AN XY: 74484

African (AFR) AF: 0.000265 AC: 11 AN: 41580

American (AMR) AF: 0.00 AC: 0 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.000282 AC: 3 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00163 AC: 111 AN: 68020

Other (OTH) AF: 0.00142 AC: 3 AN: 2108

Alfa AF: 0.000804 Hom.: 0

Bravo AF: 0.00103

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 24, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	2.6
DANN	Benign	0.51
PhyloP100		0.32
Mutation Taster		=79/21	polymorphism

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

Other links and lift over

dbSNP: rs140194920; hg19: chr17-74465794;