rs2564871

Variant names:

• chr11-112253810-C-T
• rs2564871
• NM_001145024.1:c.387-1401G>A

Variant summary

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

The NM_001145024.1(PLET1):​c.387-1401G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.705 in 152,006 control chromosomes in the GnomAD database, including 38,249 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 0.71 (38249 hom., cov: 31)
• Consequence: PLET1 NM_001145024.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0670
• Publications: 3 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.792 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLET1	NM_001145024.1	c.387-1401G>A		intron_variant	Intron 2 of 3	ENST00000338832.4	NP_001138496.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLET1	ENST00000338832.4	c.387-1401G>A		intron_variant	Intron 2 of 3	5	NM_001145024.1	ENSP00000341412.2
PTS	ENST00000531673.5	n.*364-15747C>T		intron_variant	Intron 6 of 6	1		ENSP00000433469.1

Frequencies

GnomAD3 genomes AF: 0.705 AC: 107130 AN: 151888 Hom.: 38200 Cov.: 31

Gnomad AFR AF: 0.597

Gnomad AMI AF: 0.784

Gnomad AMR AF: 0.763

Gnomad ASJ AF: 0.788

Gnomad EAS AF: 0.791

Gnomad SAS AF: 0.812

Gnomad FIN AF: 0.709

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.738

Gnomad OTH AF: 0.722

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

GnomAD4 genome AF: 0.705 AC: 107240 AN: 152006 Hom.: 38249 Cov.: 31 AF XY: 0.707 AC XY: 52505 AN XY: 74296

African (AFR) AF: 0.598 AC: 24748 AN: 41408

American (AMR) AF: 0.763 AC: 11655 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.788 AC: 2733 AN: 3470

East Asian (EAS) AF: 0.792 AC: 4091 AN: 5164

South Asian (SAS) AF: 0.813 AC: 3921 AN: 4820

European-Finnish (FIN) AF: 0.709 AC: 7492 AN: 10574

Middle Eastern (MID) AF: 0.731 AC: 215 AN: 294

European-Non Finnish (NFE) AF: 0.738 AC: 50143 AN: 67978

Other (OTH) AF: 0.724 AC: 1529 AN: 2112

Alfa AF: 0.712 Hom.: 6305

Bravo AF: 0.705

Asia WGS AF: 0.777 AC: 2701 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.8
DANN	Benign	0.65
PhyloP100		-0.067
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: rs2564871; hg19: chr11-112124533;