11-112229960-C-T

Variant names:

• chr11-112229960-C-T
• rs2518352
• NM_000317.3:c.164-248C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000317.3(PTS):​c.164-248C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.709 in 563,132 control chromosomes in the GnomAD database, including 144,651 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.65 (33440 hom., cov: 32)
  • Exomes 𝑓: 0.73 (111211 hom.)
• Consequence: PTS NM_000317.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.124
• Publications: 6 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 11-112229960-C-T is Benign according to our data. Variant chr11-112229960-C-T is described in ClinVar as Benign. ClinVar VariationId is 1258222.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.78 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000317.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTS	NM_000317.3	MANE Select	c.164-248C>T		intron	N/A	NP_000308.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PTS	ENST00000280362.8	TSL:1 MANE Select	c.164-248C>T		intron	N/A	ENSP00000280362.3
	PTS	ENST00000531673.5	TSL:1	n.164-666C>T		intron	N/A	ENSP00000433469.1
	PTS	ENST00000889305.1		c.164-248C>T		intron	N/A	ENSP00000559364.1

Frequencies

GnomAD3 genomes AF: 0.647 AC: 98311 AN: 151986 Hom.: 33420 Cov.: 32

Gnomad AFR AF: 0.420

Gnomad AMI AF: 0.781

Gnomad AMR AF: 0.731

Gnomad ASJ AF: 0.773

Gnomad EAS AF: 0.764

Gnomad SAS AF: 0.799

Gnomad FIN AF: 0.708

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.727

Gnomad OTH AF: 0.675

GnomAD4 exome AF: 0.732 AC: 300867 AN: 411028 Hom.: 111211 AF XY: 0.737 AC XY: 161387 AN XY: 219014

African (AFR) AF: 0.424 AC: 4894 AN: 11556

American (AMR) AF: 0.753 AC: 13151 AN: 17456

Ashkenazi Jewish (ASJ) AF: 0.780 AC: 9713 AN: 12448

East Asian (EAS) AF: 0.782 AC: 21700 AN: 27750

South Asian (SAS) AF: 0.783 AC: 34551 AN: 44124

European-Finnish (FIN) AF: 0.711 AC: 17363 AN: 24418

Middle Eastern (MID) AF: 0.739 AC: 1309 AN: 1772

European-Non Finnish (NFE) AF: 0.731 AC: 181195 AN: 247892

Other (OTH) AF: 0.720 AC: 16991 AN: 23612

GnomAD4 genome AF: 0.647 AC: 98361 AN: 152104 Hom.: 33440 Cov.: 32 AF XY: 0.650 AC XY: 48332 AN XY: 74366

African (AFR) AF: 0.419 AC: 17378 AN: 41440

American (AMR) AF: 0.731 AC: 11177 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.773 AC: 2680 AN: 3466

East Asian (EAS) AF: 0.765 AC: 3961 AN: 5176

South Asian (SAS) AF: 0.801 AC: 3865 AN: 4826

European-Finnish (FIN) AF: 0.708 AC: 7493 AN: 10584

Middle Eastern (MID) AF: 0.711 AC: 209 AN: 294

European-Non Finnish (NFE) AF: 0.727 AC: 49457 AN: 68008

Other (OTH) AF: 0.677 AC: 1429 AN: 2110

Alfa AF: 0.672 Hom.: 4328

Bravo AF: 0.639

Asia WGS AF: 0.740 AC: 2573 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.4
DANN	Benign	0.51
PhyloP100		0.12
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2518352; hg19: chr11-112100683;