12-71946293-G-T

Position:

• chr12-71946293-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173353.4(TPH2):​c.540+1607G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 152,032 control chromosomes in the GnomAD database, including 5,446 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 0.26 (5446 hom., cov: 32)
• Consequence: TPH2 NM_173353.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.431

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.512 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TPH2	NM_173353.4	c.540+1607G>T		intron_variant		ENST00000333850.4
TPH2	XR_001748575.2	n.682+1607G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TPH2	ENST00000333850.4	c.540+1607G>T		intron_variant		1	NM_173353.4	P1
TPH2	ENST00000546576.1	n.550+1607G>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.257 AC: 39026 AN: 151914 Hom.: 5438 Cov.: 32

Gnomad AFR AF: 0.238

Gnomad AMI AF: 0.267

Gnomad AMR AF: 0.306

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.529

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.205

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.257

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

GnomAD4 genome AF: 0.257 AC: 39065 AN: 152032 Hom.: 5446 Cov.: 32 AF XY: 0.260 AC XY: 19289 AN XY: 74326

Gnomad4 AFR AF: 0.238

Gnomad4 AMR AF: 0.306

Gnomad4 ASJ AF: 0.256

Gnomad4 EAS AF: 0.528

Gnomad4 SAS AF: 0.327

Gnomad4 FIN AF: 0.205

Gnomad4 NFE AF: 0.240

Gnomad4 OTH AF: 0.259

Alfa AF: 0.250 Hom.: 2826

Bravo AF: 0.264

Asia WGS AF: 0.423 AC: 1470 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	12
DANN	Benign	0.50

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: rs2129575; hg19: chr12-72340073;