12-71966484-A-G

Variant names:

• chr12-71966484-A-G
• rs2171363
• NM_173353.4:c.609-6035A>G

Variant summary

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

The NM_173353.4(TPH2):​c.609-6035A>G variant causes a intron change. The variant allele was found at a frequency of 0.452 in 152,086 control chromosomes in the GnomAD database, including 18,116 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 0.45 (18116 hom., cov: 32)
• Consequence: TPH2 NM_173353.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.32
• Publications: 36 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=-0.51).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.573 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173353.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPH2	NM_173353.4	MANE Select	c.609-6035A>G		intron	N/A	NP_775489.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPH2	ENST00000333850.4	TSL:1 MANE Select	c.609-6035A>G		intron	N/A	ENSP00000329093.3

Frequencies

GnomAD3 genomes AF: 0.452 AC: 68708 AN: 151968 Hom.: 18107 Cov.: 32

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.631

Gnomad AMR AF: 0.509

Gnomad ASJ AF: 0.608

Gnomad EAS AF: 0.477

Gnomad SAS AF: 0.524

Gnomad FIN AF: 0.564

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.578

Gnomad OTH AF: 0.503

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

GnomAD4 genome AF: 0.452 AC: 68731 AN: 152086 Hom.: 18116 Cov.: 32 AF XY: 0.455 AC XY: 33824 AN XY: 74350

African (AFR) AF: 0.165 AC: 6855 AN: 41552

American (AMR) AF: 0.509 AC: 7780 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.608 AC: 2105 AN: 3460

East Asian (EAS) AF: 0.477 AC: 2470 AN: 5174

South Asian (SAS) AF: 0.526 AC: 2537 AN: 4822

European-Finnish (FIN) AF: 0.564 AC: 5954 AN: 10554

Middle Eastern (MID) AF: 0.554 AC: 163 AN: 294

European-Non Finnish (NFE) AF: 0.578 AC: 39228 AN: 67918

Other (OTH) AF: 0.503 AC: 1065 AN: 2116

Alfa AF: 0.544 Hom.: 38680

Bravo AF: 0.435

Asia WGS AF: 0.477 AC: 1660 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	14
DANN	Benign	0.53
PhyloP100		4.3
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: rs2171363; hg19: chr12-72360264;