rs1386488

chr12-71950838-C-Achr12-71950838-C-Gchr12-71950838-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.608+1183C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.797 in 151,964 control chromosomes in the GnomAD database, including 48,325 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 0.80 (48325 hom., cov: 30)
• Consequence: TPH2 NM_173353.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0660

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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.821 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TPH2	NM_173353.4	c.608+1183C>A		intron_variant		ENST00000333850.4
TPH2	XR_001748575.2	n.750+1183C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TPH2	ENST00000333850.4	c.608+1183C>A		intron_variant		1	NM_173353.4	P1
TPH2	ENST00000546576.1	n.618+1183C>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.797 AC: 120978 AN: 151846 Hom.: 48278 Cov.: 30

Gnomad AFR AF: 0.738

Gnomad AMI AF: 0.895

Gnomad AMR AF: 0.833

Gnomad ASJ AF: 0.846

Gnomad EAS AF: 0.840

Gnomad SAS AF: 0.774

Gnomad FIN AF: 0.808

Gnomad MID AF: 0.820

Gnomad NFE AF: 0.816

Gnomad OTH AF: 0.811

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

GnomAD4 genome AF: 0.797 AC: 121080 AN: 151964 Hom.: 48325 Cov.: 30 AF XY: 0.798 AC XY: 59267 AN XY: 74276

Gnomad4 AFR AF: 0.739

Gnomad4 AMR AF: 0.833

Gnomad4 ASJ AF: 0.846

Gnomad4 EAS AF: 0.840

Gnomad4 SAS AF: 0.776

Gnomad4 FIN AF: 0.808

Gnomad4 NFE AF: 0.816

Gnomad4 OTH AF: 0.809

Alfa AF: 0.814 Hom.: 84098

Bravo AF: 0.797

Asia WGS AF: 0.752 AC: 2617 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	0.66
Dann	Benign	0.57

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: rs1386488; hg19: chr12-72344618;