rs12231356

Variant names:

• chr12-72015768-C-T
• rs12231356
• NM_173353.4:c.1069-6631C>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.1069-6631C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0901 in 152,068 control chromosomes in the GnomAD database, including 685 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 0.090 (685 hom., cov: 30)
• Consequence: TPH2 NM_173353.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0200
• Publications: 9 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.121 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.1069-6631C>T		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.1069-6631C>T		intron	N/A	ENSP00000329093.3

Frequencies

GnomAD3 genomes AF: 0.0899 AC: 13657 AN: 151950 Hom.: 676 Cov.: 30

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.0450

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.0528

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.0995

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0656

Gnomad OTH AF: 0.0786

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

GnomAD4 genome AF: 0.0901 AC: 13702 AN: 152068 Hom.: 685 Cov.: 30 AF XY: 0.0932 AC XY: 6932 AN XY: 74346

African (AFR) AF: 0.112 AC: 4652 AN: 41450

American (AMR) AF: 0.125 AC: 1912 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0528 AC: 183 AN: 3468

East Asian (EAS) AF: 0.129 AC: 667 AN: 5180

South Asian (SAS) AF: 0.114 AC: 550 AN: 4818

European-Finnish (FIN) AF: 0.0995 AC: 1052 AN: 10572

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0656 AC: 4459 AN: 67996

Other (OTH) AF: 0.0792 AC: 167 AN: 2108

Alfa AF: 0.0727 Hom.: 797

Bravo AF: 0.0895

Asia WGS AF: 0.132 AC: 462 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.3
DANN	Benign	0.52
PhyloP100		-0.020
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: rs12231356; hg19: chr12-72409548;