rs1386497

Positions:

• chr12-71998510-C-A
• chr12-71998510-C-G
• chr12-71998510-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.1068+3945C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.835 in 151,684 control chromosomes in the GnomAD database, including 52,911 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 0.83 (52911 hom., cov: 28)
• Consequence: TPH2 NM_173353.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.563

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.934 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TPH2	NM_173353.4	c.1068+3945C>A		intron_variant		ENST00000333850.4	NP_775489.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TPH2	ENST00000333850.4	c.1068+3945C>A		intron_variant		1	NM_173353.4	ENSP00000329093	P1

Frequencies

GnomAD3 genomes AF: 0.835 AC: 126484 AN: 151566 Hom.: 52861 Cov.: 28

Gnomad AFR AF: 0.806

Gnomad AMI AF: 0.914

Gnomad AMR AF: 0.875

Gnomad ASJ AF: 0.842

Gnomad EAS AF: 0.956

Gnomad SAS AF: 0.882

Gnomad FIN AF: 0.816

Gnomad MID AF: 0.835

Gnomad NFE AF: 0.831

Gnomad OTH AF: 0.841

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

GnomAD4 genome AF: 0.835 AC: 126593 AN: 151684 Hom.: 52911 Cov.: 28 AF XY: 0.837 AC XY: 61975 AN XY: 74086

Gnomad4 AFR AF: 0.806

Gnomad4 AMR AF: 0.875

Gnomad4 ASJ AF: 0.842

Gnomad4 EAS AF: 0.956

Gnomad4 SAS AF: 0.882

Gnomad4 FIN AF: 0.816

Gnomad4 NFE AF: 0.831

Gnomad4 OTH AF: 0.842

Alfa AF: 0.834 Hom.: 22186

Bravo AF: 0.838

Asia WGS AF: 0.907 AC: 3153 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.45
DANN	Benign	0.18

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: rs1386497; hg19: chr12-72392290;