Variant 12-72032174-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_173353.4(TPH2):c.*479G>A variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.128 in 174,672 control chromosomes in the GnomAD database, including 1,825 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1505 hom., cov: 32)

Exomes 𝑓: 0.16 ( 320 hom. )

Consequence

TPH2
NM_173353.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.71

Variant links:

Genes affected

TPH2 (HGNC:20692): (tryptophan hydroxylase 2) This gene encodes a member of the pterin-dependent aromatic acid hydroxylase family. The encoded protein catalyzes the first and rate limiting step in the biosynthesis of serotonin, an important hormone and neurotransmitter. Mutations in this gene may be associated with psychiatric diseases such as bipolar affective disorder and major depression. [provided by RefSeq, Feb 2016]

TPH2 links:

TPH2 (HGNC:):

TPH2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 12-72032174-G-A is Benign according to our data. Variant chr12-72032174-G-A is described in ClinVar as [Benign]. Clinvar id is 310397.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.239 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TPH2	NM_173353.4 linkuse as main transcript	c.*479G>A		3_prime_UTR_variant	11/11	ENST00000333850.4	NP_775489.2	Q8IWU9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TPH2	ENST00000333850.4 linkuse as main transcript	c.*479G>A		3_prime_UTR_variant	11/11	1	NM_173353.4	ENSP00000329093.3		Q8IWU9-1

Frequencies

GnomAD3 genomes

AF:

0.124

AC:

18816

AN:

151934

Hom.:

1508

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0318

Gnomad AMI

AF:

0.207

Gnomad AMR

AF:

0.180

Gnomad ASJ

AF:

0.184

Gnomad EAS

AF:

0.251

Gnomad SAS

AF:

0.179

Gnomad FIN

AF:

0.183

Gnomad MID

AF:

0.117

Gnomad NFE

AF:

0.140

Gnomad OTH

AF:

0.134

GnomAD4 exome

AF:

0.155

AC:

3507

AN:

22620

Hom.:

320

Cov.:

AF XY:

0.161

AC XY:

1887

AN XY:

11698

show subpopulations

Gnomad4 AFR exome

AF:

0.0192

Gnomad4 AMR exome

AF:

0.221

Gnomad4 ASJ exome

AF:

0.189

Gnomad4 EAS exome

AF:

0.249

Gnomad4 SAS exome

AF:

0.176

Gnomad4 FIN exome

AF:

0.139

Gnomad4 NFE exome

AF:

0.130

Gnomad4 OTH exome

AF:

0.146

GnomAD4 genome

AF:

0.124

AC:

18796

AN:

152052

Hom.:

1505

Cov.:

AF XY:

0.127

AC XY:

9440

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.0317

Gnomad4 AMR

AF:

0.179

Gnomad4 ASJ

AF:

0.184

Gnomad4 EAS

AF:

0.250

Gnomad4 SAS

AF:

0.177

Gnomad4 FIN

AF:

0.183

Gnomad4 NFE

AF:

0.140

Gnomad4 OTH

AF:

0.133

Alfa

AF:

0.141

Hom.:

709

Bravo

AF:

0.120

Asia WGS

AF:

0.194

AC:

672

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Tryptophan 5-monooxygenase deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

DANN

Benign

0.55

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.

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