12-72010598-C-T

Variant names:

• chr12-72010598-C-T
• rs1473473
• NM_173353.4:c.1069-11801C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173353.4(TPH2):​c.1069-11801C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.809 in 152,104 control chromosomes in the GnomAD database, including 49,906 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 0.81 (49906 hom., cov: 31)
• Consequence: TPH2 NM_173353.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.308
• Publications: 10 publications found

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

Our verdict: Benign. The variant received -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 = 0.906 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPH2	NM_173353.4	c.1069-11801C>T		intron_variant	Intron 8 of 10	ENST00000333850.4	NP_775489.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TPH2	ENST00000333850.4	c.1069-11801C>T		intron_variant	Intron 8 of 10	1	NM_173353.4	ENSP00000329093.3

Frequencies

GnomAD3 genomes AF: 0.809 AC: 122903 AN: 151986 Hom.: 49864 Cov.: 31

Gnomad AFR AF: 0.748

Gnomad AMI AF: 0.913

Gnomad AMR AF: 0.862

Gnomad ASJ AF: 0.837

Gnomad EAS AF: 0.928

Gnomad SAS AF: 0.874

Gnomad FIN AF: 0.782

Gnomad MID AF: 0.823

Gnomad NFE AF: 0.821

Gnomad OTH AF: 0.821

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

GnomAD4 genome AF: 0.809 AC: 123002 AN: 152104 Hom.: 49906 Cov.: 31 AF XY: 0.811 AC XY: 60312 AN XY: 74346

African (AFR) AF: 0.748 AC: 30990 AN: 41444

American (AMR) AF: 0.862 AC: 13181 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.837 AC: 2907 AN: 3472

East Asian (EAS) AF: 0.928 AC: 4810 AN: 5182

South Asian (SAS) AF: 0.874 AC: 4218 AN: 4826

European-Finnish (FIN) AF: 0.782 AC: 8261 AN: 10570

Middle Eastern (MID) AF: 0.823 AC: 242 AN: 294

European-Non Finnish (NFE) AF: 0.821 AC: 55821 AN: 68006

Other (OTH) AF: 0.823 AC: 1739 AN: 2114

Alfa AF: 0.807 Hom.: 12470

Bravo AF: 0.812

Asia WGS AF: 0.883 AC: 3069 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	0.27
DANN	Benign	0.68
PhyloP100		-0.31
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1473473; hg19: chr12-72404378;