12-71981111-G-T

Position:

• chr12-71981111-G-T

Variant summary

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

The NM_173353.4(TPH2):​c.941+2024G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.581 in 151,874 control chromosomes in the GnomAD database, including 25,904 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 0.58 (25904 hom., cov: 31)
• Consequence: TPH2 NM_173353.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.202

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.608 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TPH2	NM_173353.4	c.941+2024G>T		intron_variant		ENST00000333850.4	NP_775489.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TPH2	ENST00000333850.4	c.941+2024G>T		intron_variant		1	NM_173353.4	ENSP00000329093.3

Frequencies

GnomAD3 genomes AF: 0.581 AC: 88210 AN: 151756 Hom.: 25878 Cov.: 31

Gnomad AFR AF: 0.614

Gnomad AMI AF: 0.629

Gnomad AMR AF: 0.553

Gnomad ASJ AF: 0.627

Gnomad EAS AF: 0.470

Gnomad SAS AF: 0.528

Gnomad FIN AF: 0.564

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.579

Gnomad OTH AF: 0.588

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

GnomAD4 genome AF: 0.581 AC: 88282 AN: 151874 Hom.: 25904 Cov.: 31 AF XY: 0.579 AC XY: 42955 AN XY: 74228

Gnomad4 AFR AF: 0.614

Gnomad4 AMR AF: 0.553

Gnomad4 ASJ AF: 0.627

Gnomad4 EAS AF: 0.471

Gnomad4 SAS AF: 0.529

Gnomad4 FIN AF: 0.564

Gnomad4 NFE AF: 0.579

Gnomad4 OTH AF: 0.588

Alfa AF: 0.586 Hom.: 3234

Bravo AF: 0.583

Asia WGS AF: 0.501 AC: 1741 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.9
DANN	Benign	0.60

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: rs6582078; hg19: chr12-72374891;