chr12-71942014-A-G

Position:

• chr12-71942014-A-G

Variant summary

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

The NM_173353.4(TPH2):​c.255+281A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0975 in 152,250 control chromosomes in the GnomAD database, including 843 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 0.097 (843 hom., cov: 32)
• Consequence: TPH2 NM_173353.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0360

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]

TPH2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TPH2	NM_173353.4	c.255+281A>G		intron_variant		ENST00000333850.4	NP_775489.2
TPH2	XR_001748575.2	n.397+281A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TPH2	ENST00000333850.4	c.255+281A>G		intron_variant		1	NM_173353.4	ENSP00000329093.3
TPH2	ENST00000546576.1	n.265+281A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0973 AC: 14802 AN: 152132 Hom.: 837 Cov.: 32

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.0537

Gnomad AMR AF: 0.0874

Gnomad ASJ AF: 0.0352

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.0756

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0720

Gnomad OTH AF: 0.0845

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

GnomAD4 genome AF: 0.0975 AC: 14839 AN: 152250 Hom.: 843 Cov.: 32 AF XY: 0.0993 AC XY: 7395 AN XY: 74448

Gnomad4 AFR AF: 0.137

Gnomad4 AMR AF: 0.0880

Gnomad4 ASJ AF: 0.0352

Gnomad4 EAS AF: 0.170

Gnomad4 SAS AF: 0.177

Gnomad4 FIN AF: 0.0756

Gnomad4 NFE AF: 0.0720

Gnomad4 OTH AF: 0.0917

Alfa AF: 0.0900 Hom.: 106

Bravo AF: 0.0978

Asia WGS AF: 0.213 AC: 738 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.3
DANN	Benign	0.63

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: rs7954758; hg19: chr12-72335794;