Genetic Variant TPH1:c.*1942A>G (chr11-18019049-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004179.3(TPH1):c.*1942A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.476 in 152,042 control chromosomes in the GnomAD database, including 18,791 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.48 ( 18788 hom., cov: 32)

Exomes 𝑓: 0.57 ( 3 hom. )

Consequence

TPH1
NM_004179.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.539

Publications

6 publications found

Variant links:

Genes affected

TPH1 (HGNC:12008): (tryptophan hydroxylase 1) This gene encodes a member of the aromatic amino 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 have been associated with an elevated risk for a variety of diseases and disorders, including schizophrenia, somatic anxiety, anger-related traits, bipolar disorder, suicidal behavior, addictions, and others.[provided by RefSeq, Apr 2009]

TPH1 links:

ENSG00000255448 (HGNC:):

ENSG00000255448 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.566 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004179.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPH1	NM_004179.3	MANE Select	c.*1942A>G		3_prime_UTR	Exon 11 of 11	NP_004170.1	P17752-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TPH1	ENST00000682019.1	MANE Select	c.*1942A>G	3_prime_UTR	Exon 11 of 11	ENSP00000508368.1	P17752-1
TPH1	ENST00000250018.6	TSL:1	c.*1942A>G	3_prime_UTR	Exon 10 of 10	ENSP00000250018.2	P17752-1
TPH1	ENST00000528338.2	TSL:3	c.*1942A>G	3_prime_UTR	Exon 11 of 11	ENSP00000436081.2	E9PR49

Frequencies

GnomAD3 genomes

AF:

0.476

AC:

72357

AN:

151910

Hom.:

18788

Cov.:

show subpopulations

Gnomad AFR

AF:

0.247

Gnomad AMI

AF:

0.473

Gnomad AMR

AF:

0.536

Gnomad ASJ

AF:

0.671

Gnomad EAS

AF:

0.568

Gnomad SAS

AF:

0.495

Gnomad FIN

AF:

0.548

Gnomad MID

AF:

0.683

Gnomad NFE

AF:

0.571

Gnomad OTH

AF:

0.505

GnomAD4 exome

AF:

0.571

AC:

AN:

Hom.:

Cov.:

AF XY:

0.250

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

1.00

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.476

AC:

72373

AN:

152028

Hom.:

18788

Cov.:

AF XY:

0.475

AC XY:

35310

AN XY:

74314

show subpopulations

African (AFR)

AF:

0.247

AC:

10239

AN:

41478

American (AMR)

AF:

0.537

AC:

8199

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.671

AC:

2328

AN:

3468

East Asian (EAS)

AF:

0.568

AC:

2939

AN:

5178

South Asian (SAS)

AF:

0.495

AC:

2386

AN:

4816

European-Finnish (FIN)

AF:

0.548

AC:

5780

AN:

10554

Middle Eastern (MID)

AF:

0.679

AC:

197

AN:

290

European-Non Finnish (NFE)

AF:

0.571

AC:

38820

AN:

67958

Other (OTH)

AF:

0.501

AC:

1055

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1782

3565

5347

7130

8912

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

656

1312

1968

2624

3280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.505

Hom.:

4954

Bravo

AF:

0.465

Asia WGS

AF:

0.509

AC:

1740

AN:

3418

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

4.0

(source)

DANN

Benign

0.87

PhyloP100

-0.54

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over