rs11179000

Positions:

• chr12-71944848-A-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+162A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 152,088 control chromosomes in the GnomAD database, including 8,213 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 0.31 (8213 hom., cov: 32)
• Consequence: TPH2 NM_173353.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.685

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.517 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TPH2	NM_173353.4	c.540+162A>T		intron_variant		ENST00000333850.4	NP_775489.2
TPH2	XR_001748575.2	n.682+162A>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TPH2	ENST00000333850.4	c.540+162A>T		intron_variant		1	NM_173353.4	ENSP00000329093	P1
TPH2	ENST00000546576.1	n.550+162A>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47379 AN: 151970 Hom.: 8195 Cov.: 32

Gnomad AFR AF: 0.434

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.329

Gnomad ASJ AF: 0.266

Gnomad EAS AF: 0.534

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.236

Gnomad OTH AF: 0.296

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

GnomAD4 genome AF: 0.312 AC: 47430 AN: 152088 Hom.: 8213 Cov.: 32 AF XY: 0.312 AC XY: 23168 AN XY: 74350

Gnomad4 AFR AF: 0.435

Gnomad4 AMR AF: 0.329

Gnomad4 ASJ AF: 0.266

Gnomad4 EAS AF: 0.533

Gnomad4 SAS AF: 0.332

Gnomad4 FIN AF: 0.203

Gnomad4 NFE AF: 0.236

Gnomad4 OTH AF: 0.298

Alfa AF: 0.283 Hom.: 800

Bravo AF: 0.325

Asia WGS AF: 0.436 AC: 1516 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.20
DANN	Benign	0.23

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: rs11179000; hg19: chr12-72338628;