11-112265855-T-C

Variant names:

• chr11-112265855-T-C
• rs891360
• ENST00000531673.5:n.*364-3702T>C

Variant summary

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

The ENST00000531673.5(PTS):​n.*364-3702T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.695 in 151,974 control chromosomes in the GnomAD database, including 37,161 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 0.69 (37161 hom., cov: 31)
• Consequence: PTS ENST00000531673.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.506
• Publications: 5 publications found

Genes affected

PTS (HGNC:9689): (6-pyruvoyltetrahydropterin synthase) The enzyme encoded by this gene catalyzes the elimination of inorganic triphosphate from dihydroneopterin triphosphate, which is the second and irreversible step in the biosynthesis of tetrahydrobiopterin from GTP. Tetrahydrobiopterin, also known as BH(4), is an essential cofactor and regulator of various enzyme activities, including enzymes involved in serotonin biosynthesis and NO synthase activity. Mutations in this gene result in hyperphenylalaninemia. [provided by RefSeq, Oct 2008]

PTS Gene-Disease associations (from GenCC):

• BH4-deficient hyperphenylalaninemia A

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, ClinGen, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.781 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PTS	ENST00000531673.5	n.*364-3702T>C		intron_variant	Intron 6 of 6	1		ENSP00000433469.1

Frequencies

GnomAD3 genomes AF: 0.695 AC: 105511 AN: 151856 Hom.: 37123 Cov.: 31

Gnomad AFR AF: 0.584

Gnomad AMI AF: 0.763

Gnomad AMR AF: 0.749

Gnomad ASJ AF: 0.771

Gnomad EAS AF: 0.790

Gnomad SAS AF: 0.800

Gnomad FIN AF: 0.706

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.729

Gnomad OTH AF: 0.704

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

GnomAD4 genome AF: 0.695 AC: 105609 AN: 151974 Hom.: 37161 Cov.: 31 AF XY: 0.696 AC XY: 51695 AN XY: 74282

African (AFR) AF: 0.584 AC: 24180 AN: 41394

American (AMR) AF: 0.749 AC: 11448 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.771 AC: 2676 AN: 3472

East Asian (EAS) AF: 0.791 AC: 4068 AN: 5146

South Asian (SAS) AF: 0.802 AC: 3858 AN: 4812

European-Finnish (FIN) AF: 0.706 AC: 7459 AN: 10566

Middle Eastern (MID) AF: 0.714 AC: 210 AN: 294

European-Non Finnish (NFE) AF: 0.729 AC: 49528 AN: 67986

Other (OTH) AF: 0.706 AC: 1486 AN: 2106

Alfa AF: 0.696 Hom.: 4530

Bravo AF: 0.694

Asia WGS AF: 0.767 AC: 2668 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.8
DANN	Benign	0.55
PhyloP100		-0.51

Splicing

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

Other links and lift over

dbSNP: rs891360; hg19: chr11-112136578;