12-71972867-G-A

Variant names:

• chr12-71972867-G-A
• rs17110566
• NM_173353.4:c.805+152G>A

Variant summary

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

The NM_173353.4(TPH2):​c.805+152G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0406 in 794,336 control chromosomes in the GnomAD database, including 1,225 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 0.040 (270 hom., cov: 32)
  • Exomes 𝑓: 0.041 (955 hom.)
• Consequence: TPH2 NM_173353.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.127
• Publications: 4 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.118 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.805+152G>A		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.805+152G>A		intron	N/A	ENSP00000329093.3

Frequencies

GnomAD3 genomes AF: 0.0403 AC: 6123 AN: 152114 Hom.: 264 Cov.: 32

Gnomad AFR AF: 0.00647

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.0971

Gnomad ASJ AF: 0.00749

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.0329

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0334

Gnomad OTH AF: 0.0359

GnomAD4 exome AF: 0.0407 AC: 26118 AN: 642104 Hom.: 955 AF XY: 0.0394 AC XY: 13325 AN XY: 337932

African (AFR) AF: 0.00661 AC: 108 AN: 16346

American (AMR) AF: 0.137 AC: 3280 AN: 23960

Ashkenazi Jewish (ASJ) AF: 0.00829 AC: 132 AN: 15924

East Asian (EAS) AF: 0.132 AC: 4501 AN: 34126

South Asian (SAS) AF: 0.0299 AC: 1612 AN: 53824

European-Finnish (FIN) AF: 0.0897 AC: 2974 AN: 33166

Middle Eastern (MID) AF: 0.00816 AC: 20 AN: 2452

European-Non Finnish (NFE) AF: 0.0287 AC: 12320 AN: 429312

Other (OTH) AF: 0.0355 AC: 1171 AN: 32994

GnomAD4 genome AF: 0.0403 AC: 6129 AN: 152232 Hom.: 270 Cov.: 32 AF XY: 0.0457 AC XY: 3400 AN XY: 74430

African (AFR) AF: 0.00645 AC: 268 AN: 41564

American (AMR) AF: 0.0975 AC: 1491 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00749 AC: 26 AN: 3470

East Asian (EAS) AF: 0.126 AC: 650 AN: 5164

South Asian (SAS) AF: 0.0325 AC: 157 AN: 4826

European-Finnish (FIN) AF: 0.112 AC: 1181 AN: 10586

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0334 AC: 2271 AN: 68016

Other (OTH) AF: 0.0350 AC: 74 AN: 2114

Alfa AF: 0.0360 Hom.: 154

Bravo AF: 0.0381

Asia WGS AF: 0.0550 AC: 189 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.8
DANN	Benign	0.63
PhyloP100		-0.13
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: rs17110566; hg19: chr12-72366647;