rs11179001

chr12-71944865-G-A

Variant summary

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

The NM_173353.4(TPH2):c.540+179G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0879 in 152,202 control chromosomes in the GnomAD database, including 698 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 0.088 (698 hom., cov: 32)
• Consequence: TPH2 NM_173353.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.49

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=-0.63).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TPH2	NM_173353.4	c.540+179G>A		intron_variant		ENST00000333850.4
TPH2	XR_001748575.2	n.682+179G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TPH2	ENST00000333850.4	c.540+179G>A		intron_variant		1	NM_173353.4	P1
TPH2	ENST00000546576.1	n.550+179G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0878 AC: 13354 AN: 152084 Hom.: 694 Cov.: 32

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.0538

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.0329

Gnomad EAS AF: 0.178

Gnomad SAS AF: 0.148

Gnomad FIN AF: 0.0756

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0705

Gnomad OTH AF: 0.0714

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

GnomAD4 genome AF: 0.0879 AC: 13378 AN: 152202 Hom.: 698 Cov.: 32 AF XY: 0.0907 AC XY: 6749 AN XY: 74402

Gnomad4 AFR AF: 0.101

Gnomad4 AMR AF: 0.105

Gnomad4 ASJ AF: 0.0329

Gnomad4 EAS AF: 0.178

Gnomad4 SAS AF: 0.147

Gnomad4 FIN AF: 0.0756

Gnomad4 NFE AF: 0.0705

Gnomad4 OTH AF: 0.0749

Alfa AF: 0.0832 Hom.: 85

Bravo AF: 0.0884

Asia WGS AF: 0.187 AC: 649 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
Cadd	Benign	11
Dann	Benign	0.61

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: rs11179001; hg19: chr12-72338645;