11-112226488-C-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7

The NM_000317.3(PTS):​c.45C>T​(p.Ser15=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,434,186 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

PTS
NM_000317.3 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.423
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.28).
BP6
Variant 11-112226488-C-T is Benign according to our data. Variant chr11-112226488-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1606302.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-0.423 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PTSNM_000317.3 linkuse as main transcriptc.45C>T p.Ser15= synonymous_variant 1/6 ENST00000280362.8 NP_000308.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PTSENST00000280362.8 linkuse as main transcriptc.45C>T p.Ser15= synonymous_variant 1/61 NM_000317.3 ENSP00000280362 P1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD3 exomes
AF:
0.0000148
AC:
3
AN:
202478
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
109366
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000199
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000139
AC:
2
AN:
1434186
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
710496
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000516
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31
Bravo
AF:
0.00000756

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

6-Pyruvoyl-tetrahydrobiopterin synthase deficiency Benign:1
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJun 11, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.28
CADD
Benign
8.7
DANN
Benign
0.90
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.7

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs756084052; hg19: chr11-112097211; API