rs41265611

Variant names:

• chr12-71939143-ATCT-A
• rs41265611
• NM_173353.4:c.105+56_105+58delTCT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_173353.4(TPH2):​c.105+56_105+58delTCT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0828 in 1,354,670 control chromosomes in the GnomAD database, including 5,886 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.12 (1287 hom., cov: 30)
  • Exomes 𝑓: 0.079 (4599 hom.)
• Consequence: TPH2 NM_173353.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.331

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

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPH2	NM_173353.4	c.105+56_105+58delTCT		intron_variant	Intron 1 of 10	ENST00000333850.4	NP_775489.2
TPH2	XR_001748575.2	n.247+56_247+58delTCT		intron_variant	Intron 1 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TPH2	ENST00000333850.4	c.105+53_105+55delTCT		intron_variant	Intron 1 of 10	1	NM_173353.4	ENSP00000329093.3
TPH2	ENST00000546576.1	n.115+53_115+55delTCT		intron_variant	Intron 1 of 6	5

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17672 AN: 151982 Hom.: 1279 Cov.: 30

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.0537

Gnomad AMR AF: 0.0950

Gnomad ASJ AF: 0.0357

Gnomad EAS AF: 0.166

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.0758

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0720

Gnomad OTH AF: 0.0968

GnomAD3 exomes AF: 0.100 AC: 22249 AN: 221716 Hom.: 1413 AF XY: 0.0964 AC XY: 11577 AN XY: 120150

Gnomad AFR exome AF: 0.214

Gnomad AMR exome AF: 0.130

Gnomad ASJ exome AF: 0.0365

Gnomad EAS exome AF: 0.177

Gnomad SAS exome AF: 0.124

Gnomad FIN exome AF: 0.0674

Gnomad NFE exome AF: 0.0676

Gnomad OTH exome AF: 0.0789

GnomAD4 exome AF: 0.0785 AC: 94408 AN: 1202570 Hom.: 4599 AF XY: 0.0796 AC XY: 48609 AN XY: 610308

Gnomad4 AFR exome AF: 0.210

Gnomad4 AMR exome AF: 0.125

Gnomad4 ASJ exome AF: 0.0363

Gnomad4 EAS exome AF: 0.135

Gnomad4 SAS exome AF: 0.120

Gnomad4 FIN exome AF: 0.0713

Gnomad4 NFE exome AF: 0.0672

Gnomad4 OTH exome AF: 0.0847

GnomAD4 genome AF: 0.117 AC: 17720 AN: 152100 Hom.: 1287 Cov.: 30 AF XY: 0.117 AC XY: 8678 AN XY: 74364

Gnomad4 AFR AF: 0.211

Gnomad4 AMR AF: 0.0957

Gnomad4 ASJ AF: 0.0357

Gnomad4 EAS AF: 0.167

Gnomad4 SAS AF: 0.113

Gnomad4 FIN AF: 0.0758

Gnomad4 NFE AF: 0.0720

Gnomad4 OTH AF: 0.100

Alfa AF: 0.0885 Hom.: 135

Bravo AF: 0.122

Asia WGS AF: 0.165 AC: 571 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs41265611; hg19: chr12-72332923;