NM_173353.4:c.1069-10143G>A

Variant names:

• chr12-72012256-G-A
• rs10748190
• NM_173353.4:c.1069-10143G>A

Variant summary

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

The NM_173353.4(TPH2):​c.1069-10143G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.552 in 151,898 control chromosomes in the GnomAD database, including 23,614 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 0.55 (23614 hom., cov: 31)
• Consequence: TPH2 NM_173353.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.209
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.651 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPH2	NM_173353.4	c.1069-10143G>A		intron_variant	Intron 8 of 10	ENST00000333850.4	NP_775489.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TPH2	ENST00000333850.4	c.1069-10143G>A		intron_variant	Intron 8 of 10	1	NM_173353.4	ENSP00000329093.3

Frequencies

GnomAD3 genomes AF: 0.552 AC: 83846 AN: 151780 Hom.: 23594 Cov.: 31

Gnomad AFR AF: 0.439

Gnomad AMI AF: 0.696

Gnomad AMR AF: 0.624

Gnomad ASJ AF: 0.645

Gnomad EAS AF: 0.625

Gnomad SAS AF: 0.671

Gnomad FIN AF: 0.521

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.588

Gnomad OTH AF: 0.580

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

GnomAD4 genome AF: 0.552 AC: 83908 AN: 151898 Hom.: 23614 Cov.: 31 AF XY: 0.555 AC XY: 41203 AN XY: 74216

African (AFR) AF: 0.439 AC: 18157 AN: 41402

American (AMR) AF: 0.625 AC: 9544 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.645 AC: 2234 AN: 3466

East Asian (EAS) AF: 0.626 AC: 3230 AN: 5160

South Asian (SAS) AF: 0.670 AC: 3223 AN: 4808

European-Finnish (FIN) AF: 0.521 AC: 5500 AN: 10560

Middle Eastern (MID) AF: 0.634 AC: 185 AN: 292

European-Non Finnish (NFE) AF: 0.588 AC: 39970 AN: 67926

Other (OTH) AF: 0.584 AC: 1233 AN: 2112

Alfa AF: 0.439 Hom.: 1305

Bravo AF: 0.553

Asia WGS AF: 0.665 AC: 2314 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.1
DANN	Benign	0.32
PhyloP100		0.21
Mutation Taster		=100/0	polymorphism (auto)

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: rs10748190; hg19: chr12-72406036;