12-72013178-T-C

Variant names:

• chr12-72013178-T-C
• rs10879352
• NM_173353.4:c.1069-9221T>C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_173353.4(TPH2):​c.1069-9221T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.563 in 152,034 control chromosomes in the GnomAD database, including 24,458 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 0.56 (24458 hom., cov: 32)
• Consequence: TPH2 NM_173353.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.657 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPH2	NM_173353.4	c.1069-9221T>C		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.1069-9221T>C		intron_variant	Intron 8 of 10	1	NM_173353.4	ENSP00000329093.3

Frequencies

GnomAD3 genomes AF: 0.563 AC: 85580 AN: 151916 Hom.: 24429 Cov.: 32

Gnomad AFR AF: 0.474

Gnomad AMI AF: 0.693

Gnomad AMR AF: 0.628

Gnomad ASJ AF: 0.645

Gnomad EAS AF: 0.627

Gnomad SAS AF: 0.677

Gnomad FIN AF: 0.522

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.590

Gnomad OTH AF: 0.589

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

GnomAD4 genome AF: 0.563 AC: 85662 AN: 152034 Hom.: 24458 Cov.: 32 AF XY: 0.566 AC XY: 42069 AN XY: 74312

Gnomad4 AFR AF: 0.474

Gnomad4 AMR AF: 0.629

Gnomad4 ASJ AF: 0.645

Gnomad4 EAS AF: 0.628

Gnomad4 SAS AF: 0.676

Gnomad4 FIN AF: 0.522

Gnomad4 NFE AF: 0.590

Gnomad4 OTH AF: 0.592

Alfa AF: 0.572 Hom.: 4480

Bravo AF: 0.564

Asia WGS AF: 0.670 AC: 2330 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	13
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: rs10879352; hg19: chr12-72406958;