chr12-72061405-G-A

Position:

• chr12-72061405-G-A

Variant summary

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

The ENST00000547278.1(TPH2):​n.241-12188G>A variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 151,932 control chromosomes in the GnomAD database, including 2,042 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 0.16 (2042 hom., cov: 32)
• Consequence: TPH2 ENST00000547278.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TPH2	ENST00000547278.1	n.241-12188G>A		intron_variant, non_coding_transcript_variant		3
TPH2	ENST00000547348.5	n.202+13748G>A		intron_variant, non_coding_transcript_variant		3
TPH2	ENST00000550403.5	n.121-12188G>A		intron_variant, non_coding_transcript_variant		3
TPH2	ENST00000551074.5	n.195+13748G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24175 AN: 151814 Hom.: 2047 Cov.: 32

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.307

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.234

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.188

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.178

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

GnomAD4 genome AF: 0.159 AC: 24173 AN: 151932 Hom.: 2042 Cov.: 32 AF XY: 0.158 AC XY: 11734 AN XY: 74256

Gnomad4 AFR AF: 0.142

Gnomad4 AMR AF: 0.213

Gnomad4 ASJ AF: 0.201

Gnomad4 EAS AF: 0.233

Gnomad4 SAS AF: 0.179

Gnomad4 FIN AF: 0.122

Gnomad4 NFE AF: 0.151

Gnomad4 OTH AF: 0.177

Alfa AF: 0.154 Hom.: 227

Bravo AF: 0.168

Asia WGS AF: 0.203 AC: 705 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.043
DANN	Benign	0.45

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11179071; hg19: chr12-72455185;