12-71954918-G-T

Position:

• chr12-71954918-G-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000333850.4(TPH2):​c.608+5263G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.774 in 151,878 control chromosomes in the GnomAD database, including 46,823 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 0.77 (46823 hom., cov: 30)
• Consequence: TPH2 ENST00000333850.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.620

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.922 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TPH2	NM_173353.4	c.608+5263G>T		intron_variant		ENST00000333850.4	NP_775489.2
TPH2	XR_001748575.2	n.750+5263G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TPH2	ENST00000333850.4	c.608+5263G>T		intron_variant		1	NM_173353.4	ENSP00000329093	P1
TPH2	ENST00000546576.1	n.618+5263G>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.775 AC: 117543 AN: 151758 Hom.: 46798 Cov.: 30

Gnomad AFR AF: 0.566

Gnomad AMI AF: 0.916

Gnomad AMR AF: 0.853

Gnomad ASJ AF: 0.870

Gnomad EAS AF: 0.944

Gnomad SAS AF: 0.892

Gnomad FIN AF: 0.825

Gnomad MID AF: 0.820

Gnomad NFE AF: 0.846

Gnomad OTH AF: 0.805

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

GnomAD4 genome AF: 0.774 AC: 117612 AN: 151878 Hom.: 46823 Cov.: 30 AF XY: 0.779 AC XY: 57843 AN XY: 74258

Gnomad4 AFR AF: 0.566

Gnomad4 AMR AF: 0.853

Gnomad4 ASJ AF: 0.870

Gnomad4 EAS AF: 0.944

Gnomad4 SAS AF: 0.893

Gnomad4 FIN AF: 0.825

Gnomad4 NFE AF: 0.846

Gnomad4 OTH AF: 0.807

Alfa AF: 0.838 Hom.: 71110

Bravo AF: 0.766

Asia WGS AF: 0.897 AC: 3116 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	17
DANN	Benign	0.75

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: rs1843809; hg19: chr12-72348698;