rs10506645

Positions:

• chr12-71991720-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.942-2719C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 152,094 control chromosomes in the GnomAD database, including 4,930 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 0.25 (4930 hom., cov: 32)
• Consequence: TPH2 NM_173353.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.496

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TPH2	NM_173353.4	c.942-2719C>T		intron_variant		ENST00000333850.4	NP_775489.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TPH2	ENST00000333850.4	c.942-2719C>T		intron_variant		1	NM_173353.4	ENSP00000329093.3

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38470 AN: 151976 Hom.: 4924 Cov.: 32

Gnomad AFR AF: 0.279

Gnomad AMI AF: 0.220

Gnomad AMR AF: 0.245

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.358

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.215

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.246

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

GnomAD4 genome AF: 0.253 AC: 38491 AN: 152094 Hom.: 4930 Cov.: 32 AF XY: 0.251 AC XY: 18692 AN XY: 74352

Gnomad4 AFR AF: 0.279

Gnomad4 AMR AF: 0.244

Gnomad4 ASJ AF: 0.216

Gnomad4 EAS AF: 0.357

Gnomad4 SAS AF: 0.217

Gnomad4 FIN AF: 0.215

Gnomad4 NFE AF: 0.242

Gnomad4 OTH AF: 0.243

Alfa AF: 0.241 Hom.: 9138

Bravo AF: 0.259

Asia WGS AF: 0.234 AC: 816 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.43
DANN	Benign	0.61

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: rs10506645; hg19: chr12-72385500;