rs11179027

chr12-71983532-G-C

Variant summary

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

The NM_173353.4(TPH2):c.941+4445G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 151,996 control chromosomes in the GnomAD database, including 5,666 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 0.26 (5666 hom., cov: 31)
• Consequence: TPH2 NM_173353.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0280

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TPH2	NM_173353.4	c.941+4445G>C		intron_variant		ENST00000333850.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TPH2	ENST00000333850.4	c.941+4445G>C		intron_variant		1	NM_173353.4	P1

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40201 AN: 151878 Hom.: 5659 Cov.: 31

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.282

Gnomad AMR AF: 0.329

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.473

Gnomad SAS AF: 0.373

Gnomad FIN AF: 0.259

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.268

Gnomad OTH AF: 0.261

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

GnomAD4 genome AF: 0.265 AC: 40240 AN: 151996 Hom.: 5666 Cov.: 31 AF XY: 0.269 AC XY: 19970 AN XY: 74280

Gnomad4 AFR AF: 0.200

Gnomad4 AMR AF: 0.330

Gnomad4 ASJ AF: 0.243

Gnomad4 EAS AF: 0.472

Gnomad4 SAS AF: 0.372

Gnomad4 FIN AF: 0.259

Gnomad4 NFE AF: 0.268

Gnomad4 OTH AF: 0.263

Alfa AF: 0.265 Hom.: 675

Bravo AF: 0.266

Asia WGS AF: 0.415 AC: 1442 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.4
Dann	Benign	0.50

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: rs11179027; hg19: chr12-72377312;