chr12-71980939-T-A

Variant names:

• chr12-71980939-T-A
• rs6582076
• NM_173353.4:c.941+1852T>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.941+1852T>A 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 151,850 control chromosomes in the GnomAD database, including 25,866 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 (25866 hom., cov: 32)
• Consequence: TPH2 NM_173353.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.458
• Publications: 0 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=-0.8).
• 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 rank	MANE	Protein	UniProt
TPH2	NM_173353.4	c.941+1852T>A		intron_variant	Intron 7 of 10	ENST00000333850.4	NP_775489.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TPH2	ENST00000333850.4	c.941+1852T>A		intron_variant	Intron 7 of 10	1	NM_173353.4	ENSP00000329093.3

Frequencies

GnomAD3 genomes AF: 0.581 AC: 88163 AN: 151732 Hom.: 25840 Cov.: 32

Gnomad AFR AF: 0.614

Gnomad AMI AF: 0.629

Gnomad AMR AF: 0.552

Gnomad ASJ AF: 0.627

Gnomad EAS AF: 0.473

Gnomad SAS AF: 0.527

Gnomad FIN AF: 0.563

Gnomad MID AF: 0.618

Gnomad NFE AF: 0.579

Gnomad OTH AF: 0.590

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

GnomAD4 genome AF: 0.581 AC: 88235 AN: 151850 Hom.: 25866 Cov.: 32 AF XY: 0.578 AC XY: 42916 AN XY: 74200

African (AFR) AF: 0.614 AC: 25415 AN: 41402

American (AMR) AF: 0.552 AC: 8428 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.627 AC: 2169 AN: 3460

East Asian (EAS) AF: 0.473 AC: 2440 AN: 5156

South Asian (SAS) AF: 0.529 AC: 2543 AN: 4806

European-Finnish (FIN) AF: 0.563 AC: 5927 AN: 10526

Middle Eastern (MID) AF: 0.610 AC: 178 AN: 292

European-Non Finnish (NFE) AF: 0.579 AC: 39318 AN: 67920

Other (OTH) AF: 0.589 AC: 1245 AN: 2112

Alfa AF: 0.567 Hom.: 2517

Asia WGS AF: 0.501 AC: 1742 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.1
DANN	Benign	0.62
PhyloP100		0.46
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: rs6582076; hg19: chr12-72374719;