chr12-71972406-C-T

Position:

• chr12-71972406-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.609-113C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.553 in 967,504 control chromosomes in the GnomAD database, including 149,860 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 0.51 (20646 hom., cov: 33)
  • Exomes 𝑓: 0.56 (129214 hom.)
• Consequence: TPH2 NM_173353.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.11

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.574 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TPH2	NM_173353.4	c.609-113C>T		intron_variant		ENST00000333850.4	NP_775489.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TPH2	ENST00000333850.4	c.609-113C>T		intron_variant		1	NM_173353.4	ENSP00000329093.3

Frequencies

GnomAD3 genomes AF: 0.512 AC: 77785 AN: 151944 Hom.: 20634 Cov.: 33

Gnomad AFR AF: 0.370

Gnomad AMI AF: 0.629

Gnomad AMR AF: 0.529

Gnomad ASJ AF: 0.626

Gnomad EAS AF: 0.475

Gnomad SAS AF: 0.526

Gnomad FIN AF: 0.566

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.579

Gnomad OTH AF: 0.542

GnomAD4 exome AF: 0.560 AC: 456830 AN: 815442 Hom.: 129214 AF XY: 0.561 AC XY: 241192 AN XY: 430040

Gnomad4 AFR exome AF: 0.370

Gnomad4 AMR exome AF: 0.506

Gnomad4 ASJ exome AF: 0.640

Gnomad4 EAS exome AF: 0.514

Gnomad4 SAS exome AF: 0.528

Gnomad4 FIN exome AF: 0.575

Gnomad4 NFE exome AF: 0.576

Gnomad4 OTH exome AF: 0.553

GnomAD4 genome AF: 0.512 AC: 77823 AN: 152062 Hom.: 20646 Cov.: 33 AF XY: 0.513 AC XY: 38097 AN XY: 74334

Gnomad4 AFR AF: 0.370

Gnomad4 AMR AF: 0.529

Gnomad4 ASJ AF: 0.626

Gnomad4 EAS AF: 0.475

Gnomad4 SAS AF: 0.528

Gnomad4 FIN AF: 0.566

Gnomad4 NFE AF: 0.579

Gnomad4 OTH AF: 0.542

Alfa AF: 0.568 Hom.: 40715

Bravo AF: 0.503

Asia WGS AF: 0.489 AC: 1702 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.021
DANN	Benign	0.60

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: rs7963720; hg19: chr12-72366186;