dbSNP rs10488682: TPH1:c.-173A>T (chr11-18040935-T-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000250018.6(TPH1):c.-173A>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 687,316 control chromosomes in the GnomAD database, including 19,403 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 0.19 ( 3349 hom., cov: 32)

Exomes 𝑓: 0.24 ( 16054 hom. )

Consequence

TPH1
ENST00000250018.6 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.603

Publications

20 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:

ENSG00000302464 (HGNC:):

ENSG00000302464 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=-0.8).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPH1	NM_004179.3 link	c.-26-147A>T		intron_variant	Intron 1 of 10	ENST00000682019.1	NP_004170.1	P17752-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TPH1	ENST00000682019.1 link	c.-26-147A>T		intron_variant	Intron 1 of 10		NM_004179.3	ENSP00000508368.1		P17752-1

Frequencies

GnomAD3 genomes

AF:

0.192

AC:

29126

AN:

152018

Hom.:

3347

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0737

Gnomad AMI

AF:

0.334

Gnomad AMR

AF:

0.166

Gnomad ASJ

AF:

0.194

Gnomad EAS

AF:

0.146

Gnomad SAS

AF:

0.174

Gnomad FIN

AF:

0.297

Gnomad MID

AF:

0.168

Gnomad NFE

AF:

0.255

Gnomad OTH

AF:

0.205

GnomAD4 exome

AF:

0.237

AC:

126863

AN:

535180

Hom.:

16054

Cov.:

AF XY:

0.235

AC XY:

66434

AN XY:

282218

show subpopulations

African (AFR)

AF:

0.0699

AC:

936

AN:

13392

American (AMR)

AF:

0.167

AC:

3061

AN:

18306

Ashkenazi Jewish (ASJ)

AF:

0.196

AC:

2615

AN:

13338

East Asian (EAS)

AF:

0.116

AC:

3120

AN:

26828

South Asian (SAS)

AF:

0.181

AC:

8630

AN:

47690

European-Finnish (FIN)

AF:

0.296

AC:

7219

AN:

24428

Middle Eastern (MID)

AF:

0.242

AC:

480

AN:

1980

European-Non Finnish (NFE)

AF:

0.261

AC:

94585

AN:

361970

Other (OTH)

AF:

0.228

AC:

6217

AN:

27248

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

4578

9157

13735

18314

22892

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1636

3272

4908

6544

8180

<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:

0.191

AC:

29128

AN:

152136

Hom.:

3349

Cov.:

AF XY:

0.193

AC XY:

14337

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.0734

AC:

3051

AN:

41546

American (AMR)

AF:

0.166

AC:

2540

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.194

AC:

673

AN:

3466

East Asian (EAS)

AF:

0.146

AC:

757

AN:

5188

South Asian (SAS)

AF:

0.175

AC:

844

AN:

4814

European-Finnish (FIN)

AF:

0.297

AC:

3133

AN:

10560

Middle Eastern (MID)

AF:

0.163

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.255

AC:

17345

AN:

67962

Other (OTH)

AF:

0.205

AC:

434

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1181

2362

3544

4725

5906

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

316

632

948

1264

1580

<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:

0.220

Hom.:

514

Bravo

AF:

0.180

Asia WGS

AF:

0.163

AC:

568

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

1.9

(source)

DANN

Benign

0.75

PhyloP100

-0.60

PromoterAI

-0.00030

Neutral

(source)

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over