rs17110566

Positions:

• chr12-71972867-G-A
• chr12-71972867-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.805+152G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0406 in 794,336 control chromosomes in the GnomAD database, including 1,225 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 0.040 (270 hom., cov: 32)
  • Exomes 𝑓: 0.041 (955 hom.)
• Consequence: TPH2 NM_173353.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.127

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.118 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TPH2	NM_173353.4	c.805+152G>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.805+152G>A		intron_variant		1	NM_173353.4	ENSP00000329093	P1

Frequencies

GnomAD3 genomes AF: 0.0403 AC: 6123 AN: 152114 Hom.: 264 Cov.: 32

Gnomad AFR AF: 0.00647

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.0971

Gnomad ASJ AF: 0.00749

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.0329

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0334

Gnomad OTH AF: 0.0359

GnomAD4 exome AF: 0.0407 AC: 26118 AN: 642104 Hom.: 955 AF XY: 0.0394 AC XY: 13325 AN XY: 337932

Gnomad4 AFR exome AF: 0.00661

Gnomad4 AMR exome AF: 0.137

Gnomad4 ASJ exome AF: 0.00829

Gnomad4 EAS exome AF: 0.132

Gnomad4 SAS exome AF: 0.0299

Gnomad4 FIN exome AF: 0.0897

Gnomad4 NFE exome AF: 0.0287

Gnomad4 OTH exome AF: 0.0355

GnomAD4 genome AF: 0.0403 AC: 6129 AN: 152232 Hom.: 270 Cov.: 32 AF XY: 0.0457 AC XY: 3400 AN XY: 74430

Gnomad4 AFR AF: 0.00645

Gnomad4 AMR AF: 0.0975

Gnomad4 ASJ AF: 0.00749

Gnomad4 EAS AF: 0.126

Gnomad4 SAS AF: 0.0325

Gnomad4 FIN AF: 0.112

Gnomad4 NFE AF: 0.0334

Gnomad4 OTH AF: 0.0350

Alfa AF: 0.0412 Hom.: 64

Bravo AF: 0.0381

Asia WGS AF: 0.0550 AC: 189 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.8
DANN	Benign	0.63

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: rs17110566; hg19: chr12-72366647;