rs10506644

chr12-71961651-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173353.4(TPH2):c.609-10868A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00321 in 1,352,100 control chromosomes in the GnomAD database, including 122 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 0.016 (73 hom., cov: 33)
  • Exomes 𝑓: 0.0015 (49 hom.)
• Consequence: TPH2 NM_173353.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.302

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0559 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TPH2	NM_173353.4	c.609-10868A>G		intron_variant		ENST00000333850.4
TPH2	XR_001748575.2	n.849A>G		non_coding_transcript_exon_variant	6/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TPH2	ENST00000333850.4	c.609-10868A>G		intron_variant		1	NM_173353.4	P1
TPH2	ENST00000546576.1	n.717A>G		non_coding_transcript_exon_variant	6/7	5

Frequencies

GnomAD3 genomes AF: 0.0165 AC: 2511 AN: 152202 Hom.: 73 Cov.: 33

Gnomad AFR AF: 0.0580

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00497

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.0100

GnomAD3 exomes AF: 0.00388 AC: 890 AN: 229138 Hom.: 17 AF XY: 0.00280 AC XY: 355 AN XY: 126620

Gnomad AFR exome AF: 0.0577

Gnomad AMR exome AF: 0.00199

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000660

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000568

Gnomad OTH exome AF: 0.00154

GnomAD4 exome AF: 0.00152 AC: 1822 AN: 1199780 Hom.: 49 Cov.: 30 AF XY: 0.00127 AC XY: 758 AN XY: 594954

Gnomad4 AFR exome AF: 0.0603

Gnomad4 AMR exome AF: 0.00190

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000108

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000377

Gnomad4 OTH exome AF: 0.00260

GnomAD4 genome AF: 0.0165 AC: 2512 AN: 152320 Hom.: 73 Cov.: 33 AF XY: 0.0157 AC XY: 1171 AN XY: 74484

Gnomad4 AFR AF: 0.0578

Gnomad4 AMR AF: 0.00497

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000162

Gnomad4 OTH AF: 0.00992

Alfa AF: 0.0106 Hom.: 6

Bravo AF: 0.0188

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	2.2
Dann	Benign	0.63

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

Publications

LitVar

Other links and lift over

dbSNP: rs10506644; hg19: chr12-72355431;