rs2518360

Variant names:

• chr11-112256752-G-A
• rs2518360
• NM_001145024.1:c.185-1163C>T

Variant summary

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

The NM_001145024.1(PLET1):​c.185-1163C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.667 in 152,118 control chromosomes in the GnomAD database, including 34,912 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 0.67 (34912 hom., cov: 33)
• Consequence: PLET1 NM_001145024.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.813
• Publications: 7 publications found

Genes affected

PLET1 (HGNC:30053): (placenta expressed transcript 1) Predicted to be involved in negative regulation of cell-matrix adhesion; positive regulation of cell migration; and wound healing, spreading of epidermal cells. Predicted to be located in extracellular region and plasma membrane. Predicted to be active in apical plasma membrane and external side of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

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=-0.91).
• 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
PLET1	NM_001145024.1	c.185-1163C>T		intron_variant	Intron 1 of 3	ENST00000338832.4	NP_001138496.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLET1	ENST00000338832.4	c.185-1163C>T		intron_variant	Intron 1 of 3	5	NM_001145024.1	ENSP00000341412.2
PTS	ENST00000531673.5	n.*364-12805G>A		intron_variant	Intron 6 of 6	1		ENSP00000433469.1

Frequencies

GnomAD3 genomes AF: 0.667 AC: 101427 AN: 152000 Hom.: 34883 Cov.: 33

Gnomad AFR AF: 0.487

Gnomad AMI AF: 0.781

Gnomad AMR AF: 0.739

Gnomad ASJ AF: 0.770

Gnomad EAS AF: 0.790

Gnomad SAS AF: 0.800

Gnomad FIN AF: 0.707

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.728

Gnomad OTH AF: 0.684

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

GnomAD4 genome AF: 0.667 AC: 101510 AN: 152118 Hom.: 34912 Cov.: 33 AF XY: 0.670 AC XY: 49843 AN XY: 74360

African (AFR) AF: 0.487 AC: 20218 AN: 41480

American (AMR) AF: 0.740 AC: 11306 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.770 AC: 2675 AN: 3472

East Asian (EAS) AF: 0.791 AC: 4083 AN: 5160

South Asian (SAS) AF: 0.802 AC: 3872 AN: 4828

European-Finnish (FIN) AF: 0.707 AC: 7495 AN: 10596

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.728 AC: 49495 AN: 67984

Other (OTH) AF: 0.686 AC: 1447 AN: 2110

Alfa AF: 0.686 Hom.: 6307

Bravo AF: 0.663

Asia WGS AF: 0.759 AC: 2640 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.1
DANN	Benign	0.46
PhyloP100		0.81
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: rs2518360; hg19: chr11-112127475;