rs41317114

Variant names:

• chr12-72032569-G-C
• rs41317114
• ENST00000547278.1:n.78+1178G>C

Variant summary

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

The ENST00000547278.1(TPH2):​n.78+1178G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0885 in 151,966 control chromosomes in the GnomAD database, including 955 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 0.089 (955 hom., cov: 32)
  • Exomes 𝑓: 0.042 (0 hom.)
• Consequence: TPH2 ENST00000547278.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.502
• Publications: 3 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]

TPH2 Gene-Disease associations (from GenCC):

• attention deficit-hyperactivity disorder, susceptibility to, 7

  Inheritance: AD Classification: LIMITED Submitted by: PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000547278.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPH2	NM_173353.4	MANE Select	c.*874G>C		downstream_gene	N/A	NP_775489.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPH2	ENST00000547278.1	TSL:3	n.78+1178G>C		intron	N/A
	TPH2	ENST00000547348.5	TSL:3	n.100+1178G>C		intron	N/A
	TPH2	ENST00000550403.5	TSL:3	n.120+1178G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0884 AC: 13420 AN: 151824 Hom.: 950 Cov.: 32

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.0581

Gnomad AMR AF: 0.0634

Gnomad ASJ AF: 0.0340

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.0202

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0421

Gnomad OTH AF: 0.0705

GnomAD4 exome AF: 0.0417 AC: 1 AN: 24 Hom.: 0 AF XY: 0.0625 AC XY: 1 AN XY: 16

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0556 AC: 1 AN: 18

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0885 AC: 13450 AN: 151942 Hom.: 955 Cov.: 32 AF XY: 0.0873 AC XY: 6482 AN XY: 74288

African (AFR) AF: 0.187 AC: 7751 AN: 41410

American (AMR) AF: 0.0632 AC: 963 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.0340 AC: 118 AN: 3472

East Asian (EAS) AF: 0.129 AC: 670 AN: 5178

South Asian (SAS) AF: 0.132 AC: 635 AN: 4818

European-Finnish (FIN) AF: 0.0202 AC: 214 AN: 10596

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0421 AC: 2861 AN: 67922

Other (OTH) AF: 0.0779 AC: 164 AN: 2106

Alfa AF: 0.0662 Hom.: 61

Bravo AF: 0.0958

Asia WGS AF: 0.159 AC: 555 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.1
DANN	Benign	0.70
PhyloP100		-0.50

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs41317114; hg19: chr12-72426349;