12-72010598-C-T

Position:

• chr12-72010598-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.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

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 = 0.906 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TPH2	NM_173353.4	c.1069-11801C>T		intron_variant		ENST00000333850.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TPH2	ENST00000333850.4	c.1069-11801C>T		intron_variant		1	NM_173353.4	P1

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

Gnomad4 AFR AF: 0.748

Gnomad4 AMR AF: 0.862

Gnomad4 ASJ AF: 0.837

Gnomad4 EAS AF: 0.928

Gnomad4 SAS AF: 0.874

Gnomad4 FIN AF: 0.782

Gnomad4 NFE AF: 0.821

Gnomad4 OTH AF: 0.823

Alfa AF: 0.771 Hom.: 3657

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

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: rs1473473; hg19: chr12-72404378;