chr12-72022214-A-G

Variant names:

• chr12-72022214-A-G
• rs11615016
• NM_173353.4:c.1069-185A>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.1069-185A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0522 in 152,268 control chromosomes in the GnomAD database, including 317 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 0.052 (317 hom., cov: 32)
• Consequence: TPH2 NM_173353.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.89
• Publications: 6 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0823 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.1069-185A>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.1069-185A>G		intron	N/A	ENSP00000329093.3

Frequencies

GnomAD3 genomes AF: 0.0522 AC: 7939 AN: 152150 Hom.: 316 Cov.: 32

Gnomad AFR AF: 0.0163

Gnomad AMI AF: 0.0868

Gnomad AMR AF: 0.0424

Gnomad ASJ AF: 0.0867

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.0190

Gnomad FIN AF: 0.0258

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0841

Gnomad OTH AF: 0.0579

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

GnomAD4 genome AF: 0.0522 AC: 7941 AN: 152268 Hom.: 317 Cov.: 32 AF XY: 0.0486 AC XY: 3620 AN XY: 74458

African (AFR) AF: 0.0162 AC: 675 AN: 41568

American (AMR) AF: 0.0423 AC: 647 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0867 AC: 301 AN: 3472

East Asian (EAS) AF: 0.000385 AC: 2 AN: 5190

South Asian (SAS) AF: 0.0201 AC: 97 AN: 4826

European-Finnish (FIN) AF: 0.0258 AC: 274 AN: 10608

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0841 AC: 5718 AN: 67998

Other (OTH) AF: 0.0578 AC: 122 AN: 2112

Alfa AF: 0.0698 Hom.: 383

Bravo AF: 0.0543

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.039
DANN	Benign	0.46
PhyloP100		-2.9
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: rs11615016; hg19: chr12-72415994;