12-71968485-C-T

Variant summary

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

The NM_173353.4(TPH2):c.609-4034C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.712 in 152,128 control chromosomes in the GnomAD database, including 40,331 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 0.71 (40331 hom., cov: 32)
• Consequence: TPH2 NM_173353.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0510

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.813 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TPH2	NM_173353.4	c.609-4034C>T		intron_variant		ENST00000333850.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TPH2	ENST00000333850.4	c.609-4034C>T		intron_variant		1	NM_173353.4	P1

Frequencies

GnomAD3 genomes AF: 0.713 AC: 108320 AN: 152010 Hom.: 40321 Cov.: 32

Gnomad AFR AF: 0.474

Gnomad AMI AF: 0.851

Gnomad AMR AF: 0.755

Gnomad ASJ AF: 0.838

Gnomad EAS AF: 0.816

Gnomad SAS AF: 0.729

Gnomad FIN AF: 0.780

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.819

Gnomad OTH AF: 0.747

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

GnomAD4 genome AF: 0.712 AC: 108360 AN: 152128 Hom.: 40331 Cov.: 32 AF XY: 0.713 AC XY: 53023 AN XY: 74386

Gnomad4 AFR AF: 0.474

Gnomad4 AMR AF: 0.754

Gnomad4 ASJ AF: 0.838

Gnomad4 EAS AF: 0.816

Gnomad4 SAS AF: 0.732

Gnomad4 FIN AF: 0.780

Gnomad4 NFE AF: 0.819

Gnomad4 OTH AF: 0.745

Alfa AF: 0.768 Hom.: 6473

Bravo AF: 0.703

Asia WGS AF: 0.706 AC: 2455 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	2.1
Dann	Benign	0.70

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: rs1386492; hg19: chr12-72362265;