Variant 12-71979082-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_173353.4(TPH2):c.936A>G(p.Pro312=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.57 in 1,613,674 control chromosomes in the GnomAD database, including 263,420 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.58 ( 25593 hom., cov: 31)

Exomes 𝑓: 0.57 ( 237827 hom. )

Consequence

TPH2
NM_173353.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.88

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BP6

Variant 12-71979082-A-G is Benign according to our data. Variant chr12-71979082-A-G is described in ClinVar as [Benign]. Clinvar id is 310386.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.88 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.595 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.936A>G	p.Pro312=	synonymous_variant	7/11	ENST00000333850.4	NP_775489.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TPH2	ENST00000333850.4 linkuse as main transcript	c.936A>G	p.Pro312=	synonymous_variant	7/11	1	NM_173353.4	ENSP00000329093	P1	Q8IWU9-1

Frequencies

GnomAD3 genomes

AF:

0.578

AC:

87733

AN:

151842

Hom.:

25569

Cov.:

show subpopulations

Gnomad AFR

AF:

0.602

Gnomad AMI

AF:

0.630

Gnomad AMR

AF:

0.551

Gnomad ASJ

AF:

0.627

Gnomad EAS

AF:

0.472

Gnomad SAS

AF:

0.527

Gnomad FIN

AF:

0.564

Gnomad MID

AF:

0.614

Gnomad NFE

AF:

0.579

Gnomad OTH

AF:

0.587

GnomAD3 exomes

AF:

0.562

AC:

141284

AN:

251440

Hom.:

40161

AF XY:

0.562

AC XY:

76412

AN XY:

135896

show subpopulations

Gnomad AFR exome

AF:

0.602

Gnomad AMR exome

AF:

0.518

Gnomad ASJ exome

AF:

0.642

Gnomad EAS exome

AF:

0.469

Gnomad SAS exome

AF:

0.533

Gnomad FIN exome

AF:

0.576

Gnomad NFE exome

AF:

0.582

Gnomad OTH exome

AF:

0.578

GnomAD4 exome

AF:

0.569

AC:

832204

AN:

1461714

Hom.:

237827

Cov.:

AF XY:

0.568

AC XY:

413322

AN XY:

727184

show subpopulations

Gnomad4 AFR exome

AF:

0.602

Gnomad4 AMR exome

AF:

0.518

Gnomad4 ASJ exome

AF:

0.641

Gnomad4 EAS exome

AF:

0.511

Gnomad4 SAS exome

AF:

0.529

Gnomad4 FIN exome

AF:

0.575

Gnomad4 NFE exome

AF:

0.574

Gnomad4 OTH exome

AF:

0.566

GnomAD4 genome

AF:

0.578

AC:

87798

AN:

151960

Hom.:

25593

Cov.:

AF XY:

0.575

AC XY:

42720

AN XY:

74264

show subpopulations

Gnomad4 AFR

AF:

0.601

Gnomad4 AMR

AF:

0.551

Gnomad4 ASJ

AF:

0.627

Gnomad4 EAS

AF:

0.472

Gnomad4 SAS

AF:

0.529

Gnomad4 FIN

AF:

0.564

Gnomad4 NFE

AF:

0.579

Gnomad4 OTH

AF:

0.587

Alfa

AF:

0.580

Hom.:

40420

Bravo

AF:

0.579

Asia WGS

AF:

0.499

AC:

1736

AN:

3478

EpiCase

AF:

0.589

EpiControl

AF:

0.585

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

Mar 06, 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

-0.96

CADD

Benign

0.015

DANN

Benign

0.41

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