rs2200579

Positions:

• chr12-72016965-G-A
• chr12-72016965-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173353.4(TPH2):​c.1069-5434G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.535 in 151,898 control chromosomes in the GnomAD database, including 22,589 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 0.54 (22589 hom., cov: 31)
• Consequence: TPH2 NM_173353.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.210

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.621 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TPH2	NM_173353.4	c.1069-5434G>A		intron_variant		ENST00000333850.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TPH2	ENST00000333850.4	c.1069-5434G>A		intron_variant		1	NM_173353.4	P1

Frequencies

GnomAD3 genomes AF: 0.535 AC: 81243 AN: 151780 Hom.: 22587 Cov.: 31

Gnomad AFR AF: 0.393

Gnomad AMI AF: 0.662

Gnomad AMR AF: 0.544

Gnomad ASJ AF: 0.607

Gnomad EAS AF: 0.474

Gnomad SAS AF: 0.486

Gnomad FIN AF: 0.503

Gnomad MID AF: 0.548

Gnomad NFE AF: 0.626

Gnomad OTH AF: 0.568

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.535 AC: 81274 AN: 151898 Hom.: 22589 Cov.: 31 AF XY: 0.530 AC XY: 39366 AN XY: 74246

Gnomad4 AFR AF: 0.393

Gnomad4 AMR AF: 0.544

Gnomad4 ASJ AF: 0.607

Gnomad4 EAS AF: 0.475

Gnomad4 SAS AF: 0.488

Gnomad4 FIN AF: 0.503

Gnomad4 NFE AF: 0.626

Gnomad4 OTH AF: 0.565

Alfa AF: 0.597 Hom.: 6418

Bravo AF: 0.533

Asia WGS AF: 0.464 AC: 1613 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.92
DANN	Benign	0.57

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

Other links and lift over

dbSNP: rs2200579; hg19: chr12-72410745;