rs778736284

chr11-112228588-G-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_000317.3(PTS):c.84-6G>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0011 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00063 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PTS NM_000317.3 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00005112
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.39

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]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 11-112228588-G-T is Benign according to our data. Variant chr11-112228588-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 463154.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PTS	NM_000317.3	c.84-6G>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000280362.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PTS	ENST00000280362.8	c.84-6G>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_000317.3	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 128 AN: 120914 Hom.: 0 Cov.: 31 FAILED QC

Gnomad AFR AF: 0.00103

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000678

Gnomad ASJ AF: 0.00103

Gnomad EAS AF: 0.000689

Gnomad SAS AF: 0.000521

Gnomad FIN AF: 0.00623

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000653

Gnomad OTH AF: 0.000614

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000634 AC: 777 AN: 1224840 Hom.: 0 Cov.: 33 AF XY: 0.000620 AC XY: 374 AN XY: 602992

Gnomad4 AFR exome AF: 0.00247

Gnomad4 AMR exome AF: 0.0127

Gnomad4 ASJ exome AF: 0.00194

Gnomad4 EAS exome AF: 0.000367

Gnomad4 SAS exome AF: 0.00167

Gnomad4 FIN exome AF: 0.00103

Gnomad4 NFE exome AF: 0.000223

Gnomad4 OTH exome AF: 0.000738

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00108 AC: 131 AN: 120968 Hom.: 0 Cov.: 31 AF XY: 0.00125 AC XY: 73 AN XY: 58258

Gnomad4 AFR AF: 0.00109

Gnomad4 AMR AF: 0.000677

Gnomad4 ASJ AF: 0.00103

Gnomad4 EAS AF: 0.000692

Gnomad4 SAS AF: 0.000783

Gnomad4 FIN AF: 0.00623

Gnomad4 NFE AF: 0.000653

Gnomad4 OTH AF: 0.000608

Alfa AF: 0.00143 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

6-Pyruvoyl-tetrahydrobiopterin synthase deficiency Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 13, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	0.051
Dann	Benign	0.58
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000051
dbscSNV1_RF	Benign	0.096
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: rs778736284; hg19: chr11-112099311; COSMIC: COSV54786091; COSMIC: COSV54786091;