12-71972859-G-T

Position:

• chr12-71972859-G-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_173353.4(TPH2):​c.805+144G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00117 in 835,920 control chromosomes in the GnomAD database, including 9 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 0.0044 (6 hom., cov: 32)
  • Exomes 𝑓: 0.00046 (3 hom.)
• Consequence: TPH2 NM_173353.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0860

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.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BS2: High AC in GnomAd4 at 667 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TPH2	NM_173353.4	c.805+144G>T		intron_variant		ENST00000333850.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TPH2	ENST00000333850.4	c.805+144G>T		intron_variant		1	NM_173353.4	P1

Frequencies

GnomAD3 genomes AF: 0.00438 AC: 666 AN: 152016 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.0153

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00184

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: 0.0000147

Gnomad OTH AF: 0.00144

GnomAD4 exome AF: 0.000456 AC: 312 AN: 683788 Hom.: 3 AF XY: 0.000380 AC XY: 136 AN XY: 357930

Gnomad4 AFR exome AF: 0.0150

Gnomad4 AMR exome AF: 0.00104

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000108

Gnomad4 OTH exome AF: 0.000668

GnomAD4 genome AF: 0.00438 AC: 667 AN: 152132 Hom.: 6 Cov.: 32 AF XY: 0.00428 AC XY: 318 AN XY: 74374

Gnomad4 AFR AF: 0.0153

Gnomad4 AMR AF: 0.00190

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.0000565 Hom.: 10

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.6
DANN	Benign	0.28

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: rs10879348; hg19: chr12-72366639;