chr12-71972859-G-A

Position:

• chr12-71972859-G-A

Variant summary

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

The NM_173353.4(TPH2):​c.805+144G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0489 in 835,682 control chromosomes in the GnomAD database, including 2,007 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 0.062 (457 hom., cov: 32)
  • Exomes 𝑓: 0.046 (1550 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0616 AC: 9358 AN: 151988 Hom.: 444 Cov.: 32

Gnomad AFR AF: 0.0926

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.0980

Gnomad ASJ AF: 0.0277

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.0441

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0269

Gnomad OTH AF: 0.0542

GnomAD4 exome AF: 0.0460 AC: 31428 AN: 683578 Hom.: 1550 AF XY: 0.0500 AC XY: 17907 AN XY: 357818

Gnomad4 AFR exome AF: 0.0943

Gnomad4 AMR exome AF: 0.112

Gnomad4 ASJ exome AF: 0.0240

Gnomad4 EAS exome AF: 0.100

Gnomad4 SAS exome AF: 0.156

Gnomad4 FIN exome AF: 0.0383

Gnomad4 NFE exome AF: 0.0243

Gnomad4 OTH exome AF: 0.0493

GnomAD4 genome AF: 0.0618 AC: 9403 AN: 152104 Hom.: 457 Cov.: 32 AF XY: 0.0663 AC XY: 4932 AN XY: 74362

Gnomad4 AFR AF: 0.0932

Gnomad4 AMR AF: 0.0986

Gnomad4 ASJ AF: 0.0277

Gnomad4 EAS AF: 0.126

Gnomad4 SAS AF: 0.167

Gnomad4 FIN AF: 0.0441

Gnomad4 NFE AF: 0.0269

Gnomad4 OTH AF: 0.0579

Alfa AF: 0.0152 Hom.: 10

Bravo AF: 0.0643

Asia WGS AF: 0.195 AC: 676 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.7
DANN	Benign	0.24

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;