chr12-71978821-C-T

Position:

• chr12-71978821-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.806-131C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.568 in 1,099,092 control chromosomes in the GnomAD database, including 178,625 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 0.57 (25194 hom., cov: 33)
  • Exomes 𝑓: 0.57 (153431 hom.)
• Consequence: TPH2 NM_173353.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.834

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=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.579 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TPH2	NM_173353.4	c.806-131C>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.806-131C>T		intron_variant		1	NM_173353.4	ENSP00000329093.3

Frequencies

GnomAD3 genomes AF: 0.573 AC: 87120 AN: 151960 Hom.: 25173 Cov.: 33

Gnomad AFR AF: 0.586

Gnomad AMI AF: 0.632

Gnomad AMR AF: 0.550

Gnomad ASJ AF: 0.627

Gnomad EAS AF: 0.472

Gnomad SAS AF: 0.527

Gnomad FIN AF: 0.565

Gnomad MID AF: 0.615

Gnomad NFE AF: 0.579

Gnomad OTH AF: 0.585

GnomAD4 exome AF: 0.567 AC: 537005 AN: 947014 Hom.: 153431 AF XY: 0.566 AC XY: 278881 AN XY: 492640

Gnomad4 AFR exome AF: 0.583

Gnomad4 AMR exome AF: 0.516

Gnomad4 ASJ exome AF: 0.641

Gnomad4 EAS exome AF: 0.512

Gnomad4 SAS exome AF: 0.528

Gnomad4 FIN exome AF: 0.575

Gnomad4 NFE exome AF: 0.574

Gnomad4 OTH exome AF: 0.567

GnomAD4 genome AF: 0.573 AC: 87183 AN: 152078 Hom.: 25194 Cov.: 33 AF XY: 0.571 AC XY: 42451 AN XY: 74338

Gnomad4 AFR AF: 0.586

Gnomad4 AMR AF: 0.550

Gnomad4 ASJ AF: 0.627

Gnomad4 EAS AF: 0.472

Gnomad4 SAS AF: 0.528

Gnomad4 FIN AF: 0.565

Gnomad4 NFE AF: 0.579

Gnomad4 OTH AF: 0.585

Alfa AF: 0.582 Hom.: 44646

Bravo AF: 0.574

Asia WGS AF: 0.499 AC: 1736 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	9.5
DANN	Benign	0.42

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: rs4760816; hg19: chr12-72372601;