rs1386498

Variant names:

• chr12-72004363-A-C
• rs1386498
• NM_173353.4:c.1068+9798A>C

Your query was ambiguous. Multiple possible variants found:

• chr12-72004363-A-C
• chr12-72004363-A-G
• chr12-72004363-A-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_173353.4(TPH2):​c.1068+9798A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.0 (0 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: TPH2 NM_173353.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.37
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPH2	NM_173353.4	MANE Select	c.1068+9798A>C		intron	N/A	NP_775489.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPH2	ENST00000333850.4	TSL:1 MANE Select	c.1068+9798A>C		intron	N/A	ENSP00000329093.3	Q8IWU9-1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 149904 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.00

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 149904 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 72914

African (AFR) AF: 0.00 AC: 0 AN: 41018

American (AMR) AF: 0.00 AC: 0 AN: 14724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3460

East Asian (EAS) AF: 0.00 AC: 0 AN: 4896

South Asian (SAS) AF: 0.00 AC: 0 AN: 4426

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10392

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 310

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67714

Other (OTH) AF: 0.00 AC: 0 AN: 2056

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.057
DANN	Benign	0.44
PhyloP100		-2.4

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: rs1386498; hg19: chr12-72398143;