rs10879357

Variant names:

• chr12-72020783-A-G
• rs10879357
• NM_173353.4:c.1069-1616A>G

Variant summary

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

The NM_173353.4(TPH2):​c.1069-1616A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.586 in 151,938 control chromosomes in the GnomAD database, including 26,246 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 0.59 (26246 hom., cov: 31)
• Consequence: TPH2 NM_173353.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.57
• Publications: 24 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=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.604 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPH2	NM_173353.4	c.1069-1616A>G		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.1069-1616A>G		intron_variant	Intron 8 of 10	1	NM_173353.4	ENSP00000329093.3

Frequencies

GnomAD3 genomes AF: 0.586 AC: 88969 AN: 151822 Hom.: 26217 Cov.: 31

Gnomad AFR AF: 0.592

Gnomad AMI AF: 0.646

Gnomad AMR AF: 0.569

Gnomad ASJ AF: 0.593

Gnomad EAS AF: 0.493

Gnomad SAS AF: 0.527

Gnomad FIN AF: 0.497

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.609

Gnomad OTH AF: 0.593

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

GnomAD4 genome AF: 0.586 AC: 89051 AN: 151938 Hom.: 26246 Cov.: 31 AF XY: 0.580 AC XY: 43107 AN XY: 74272

African (AFR) AF: 0.593 AC: 24539 AN: 41408

American (AMR) AF: 0.569 AC: 8688 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.593 AC: 2057 AN: 3468

East Asian (EAS) AF: 0.494 AC: 2549 AN: 5162

South Asian (SAS) AF: 0.528 AC: 2540 AN: 4812

European-Finnish (FIN) AF: 0.497 AC: 5254 AN: 10564

Middle Eastern (MID) AF: 0.629 AC: 185 AN: 294

European-Non Finnish (NFE) AF: 0.609 AC: 41406 AN: 67946

Other (OTH) AF: 0.591 AC: 1245 AN: 2108

Alfa AF: 0.604 Hom.: 61678

Bravo AF: 0.591

Asia WGS AF: 0.498 AC: 1734 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.46
DANN	Benign	0.56
PhyloP100		-1.6
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: rs10879357; hg19: chr12-72414563;