12-71968485-C-T

Variant names:

• chr12-71968485-C-T
• rs1386492
• NM_173353.4:c.609-4034C>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.609-4034C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.712 in 152,128 control chromosomes in the GnomAD database, including 40,331 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 0.71 (40331 hom., cov: 32)
• Consequence: TPH2 NM_173353.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0510
• Publications: 13 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.813 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPH2	NM_173353.4	c.609-4034C>T		intron_variant	Intron 5 of 10	ENST00000333850.4	NP_775489.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TPH2	ENST00000333850.4	c.609-4034C>T		intron_variant	Intron 5 of 10	1	NM_173353.4	ENSP00000329093.3

Frequencies

GnomAD3 genomes AF: 0.713 AC: 108320 AN: 152010 Hom.: 40321 Cov.: 32

Gnomad AFR AF: 0.474

Gnomad AMI AF: 0.851

Gnomad AMR AF: 0.755

Gnomad ASJ AF: 0.838

Gnomad EAS AF: 0.816

Gnomad SAS AF: 0.729

Gnomad FIN AF: 0.780

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.819

Gnomad OTH AF: 0.747

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

GnomAD4 genome AF: 0.712 AC: 108360 AN: 152128 Hom.: 40331 Cov.: 32 AF XY: 0.713 AC XY: 53023 AN XY: 74386

African (AFR) AF: 0.474 AC: 19631 AN: 41450

American (AMR) AF: 0.754 AC: 11541 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.838 AC: 2911 AN: 3472

East Asian (EAS) AF: 0.816 AC: 4208 AN: 5154

South Asian (SAS) AF: 0.732 AC: 3529 AN: 4824

European-Finnish (FIN) AF: 0.780 AC: 8272 AN: 10606

Middle Eastern (MID) AF: 0.776 AC: 228 AN: 294

European-Non Finnish (NFE) AF: 0.819 AC: 55690 AN: 68000

Other (OTH) AF: 0.745 AC: 1574 AN: 2114

Alfa AF: 0.768 Hom.: 6473

Bravo AF: 0.703

Asia WGS AF: 0.706 AC: 2455 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.1
DANN	Benign	0.70
PhyloP100		0.051
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: rs1386492; hg19: chr12-72362265;