12-72020937-C-T

Variant names:

• chr12-72020937-C-T
• rs4469933
• NM_173353.4:c.1069-1462C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173353.4(TPH2):​c.1069-1462C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.527 in 151,890 control chromosomes in the GnomAD database, including 22,411 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 0.53 (22411 hom., cov: 31)
• Consequence: TPH2 NM_173353.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0290
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPH2	NM_173353.4	c.1069-1462C>T		intron_variant	Intron 8 of 10	ENST00000333850.4	NP_775489.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TPH2	ENST00000333850.4	c.1069-1462C>T		intron_variant	Intron 8 of 10	1	NM_173353.4	ENSP00000329093.3

Frequencies

GnomAD3 genomes AF: 0.527 AC: 80037 AN: 151772 Hom.: 22403 Cov.: 31

Gnomad AFR AF: 0.337

Gnomad AMI AF: 0.666

Gnomad AMR AF: 0.547

Gnomad ASJ AF: 0.609

Gnomad EAS AF: 0.479

Gnomad SAS AF: 0.518

Gnomad FIN AF: 0.510

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.638

Gnomad OTH AF: 0.561

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

GnomAD4 genome AF: 0.527 AC: 80078 AN: 151890 Hom.: 22411 Cov.: 31 AF XY: 0.523 AC XY: 38821 AN XY: 74266

African (AFR) AF: 0.337 AC: 13968 AN: 41422

American (AMR) AF: 0.547 AC: 8332 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.609 AC: 2113 AN: 3472

East Asian (EAS) AF: 0.479 AC: 2477 AN: 5166

South Asian (SAS) AF: 0.520 AC: 2501 AN: 4814

European-Finnish (FIN) AF: 0.510 AC: 5371 AN: 10540

Middle Eastern (MID) AF: 0.612 AC: 180 AN: 294

European-Non Finnish (NFE) AF: 0.638 AC: 43349 AN: 67930

Other (OTH) AF: 0.559 AC: 1180 AN: 2112

Alfa AF: 0.604 Hom.: 18233

Bravo AF: 0.522

Asia WGS AF: 0.476 AC: 1656 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.1
DANN	Benign	0.20
PhyloP100		-0.029
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4469933; hg19: chr12-72414717;