rs17110747

Variant names:

• chr12-72032174-G-A
• rs17110747
• NM_173353.4:c.*479G>A

Your query was ambiguous. Multiple possible variants found:

• chr12-72032174-G-A
• chr12-72032174-G-C
• chr12-72032174-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_173353.4(TPH2):​c.*479G>A variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.128 in 174,672 control chromosomes in the GnomAD database, including 1,825 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1505 hom., cov: 32)
  • Exomes 𝑓: 0.16 (320 hom.)
• Consequence: TPH2 NM_173353.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.71
• Publications: 35 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 12-72032174-G-A is Benign according to our data. Variant chr12-72032174-G-A is described in ClinVar as Benign. ClinVar VariationId is 310397.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.239 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPH2	NM_173353.4	c.*479G>A		3_prime_UTR_variant	Exon 11 of 11	ENST00000333850.4	NP_775489.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TPH2	ENST00000333850.4	c.*479G>A		3_prime_UTR_variant	Exon 11 of 11	1	NM_173353.4	ENSP00000329093.3

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18816 AN: 151934 Hom.: 1508 Cov.: 32

Gnomad AFR AF: 0.0318

Gnomad AMI AF: 0.207

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.251

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.134

GnomAD4 exome AF: 0.155 AC: 3507 AN: 22620 Hom.: 320 Cov.: 0 AF XY: 0.161 AC XY: 1887 AN XY: 11698

African (AFR) AF: 0.0192 AC: 9 AN: 468

American (AMR) AF: 0.221 AC: 613 AN: 2776

Ashkenazi Jewish (ASJ) AF: 0.189 AC: 89 AN: 470

East Asian (EAS) AF: 0.249 AC: 396 AN: 1588

South Asian (SAS) AF: 0.176 AC: 456 AN: 2590

European-Finnish (FIN) AF: 0.139 AC: 102 AN: 734

Middle Eastern (MID) AF: 0.159 AC: 7 AN: 44

European-Non Finnish (NFE) AF: 0.130 AC: 1675 AN: 12852

Other (OTH) AF: 0.146 AC: 160 AN: 1098

GnomAD4 genome AF: 0.124 AC: 18796 AN: 152052 Hom.: 1505 Cov.: 32 AF XY: 0.127 AC XY: 9440 AN XY: 74312

African (AFR) AF: 0.0317 AC: 1316 AN: 41528

American (AMR) AF: 0.179 AC: 2738 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 638 AN: 3468

East Asian (EAS) AF: 0.250 AC: 1289 AN: 5156

South Asian (SAS) AF: 0.177 AC: 857 AN: 4830

European-Finnish (FIN) AF: 0.183 AC: 1928 AN: 10550

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.140 AC: 9525 AN: 67952

Other (OTH) AF: 0.133 AC: 280 AN: 2108

Alfa AF: 0.142 Hom.: 1115

Bravo AF: 0.120

Asia WGS AF: 0.194 AC: 672 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Tryptophan 5-monooxygenase deficiency Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	11
DANN	Benign	0.55
PhyloP100		3.7
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: rs17110747; hg19: chr12-72425954;