dbSNP rs41317114: TPH2:n.78+1178G>C (chr12-72032569-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000547278.1(TPH2):n.78+1178G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0885 in 151,966 control chromosomes in the GnomAD database, including 955 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 0.089 ( 955 hom., cov: 32)

Exomes 𝑓: 0.042 ( 0 hom. )

Consequence

TPH2
ENST00000547278.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.502

Publications

3 publications found

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 was made for transcript

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

BP4

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

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPH2	NM_173353.4 link	c.*874G>C		downstream_gene_variant		ENST00000333850.4	NP_775489.2	Q8IWU9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TPH2	ENST00000333850.4 link	c.*874G>C		downstream_gene_variant		1	NM_173353.4	ENSP00000329093.3		Q8IWU9-1

Frequencies

GnomAD3 genomes

AF:

0.0884

AC:

13420

AN:

151824

Hom.:

950

Cov.:

show subpopulations

Gnomad AFR

AF:

0.187

Gnomad AMI

AF:

0.0581

Gnomad AMR

AF:

0.0634

Gnomad ASJ

AF:

0.0340

Gnomad EAS

AF:

0.129

Gnomad SAS

AF:

0.134

Gnomad FIN

AF:

0.0202

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.0421

Gnomad OTH

AF:

0.0705

GnomAD4 exome

AF:

0.0417

AC:

AN:

Hom.:

AF XY:

0.0625

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0556

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0885

AC:

13450

AN:

151942

Hom.:

955

Cov.:

AF XY:

0.0873

AC XY:

6482

AN XY:

74288

show subpopulations

African (AFR)

AF:

0.187

AC:

7751

AN:

41410

American (AMR)

AF:

0.0632

AC:

963

AN:

15234

Ashkenazi Jewish (ASJ)

AF:

0.0340

AC:

118

AN:

3472

East Asian (EAS)

AF:

0.129

AC:

670

AN:

5178

South Asian (SAS)

AF:

0.132

AC:

635

AN:

4818

European-Finnish (FIN)

AF:

0.0202

AC:

214

AN:

10596

Middle Eastern (MID)

AF:

0.0714

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0421

AC:

2861

AN:

67922

Other (OTH)

AF:

0.0779

AC:

164

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

573

1147

1720

2294

2867

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

154

308

462

616

770

<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:

0.0662

Hom.:

Bravo

AF:

0.0958

Asia WGS

AF:

0.159

AC:

555

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

2.1

(source)

DANN

Benign

0.70

PhyloP100

-0.50

Splicing

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over