11-112253810-C-T

Position:

• chr11-112253810-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
PLET1	NM_001145024.1	c.387-1401G>A		intron_variant		ENST00000338832.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLET1	ENST00000338832.4	c.387-1401G>A		intron_variant		5	NM_001145024.1	P1
PTS	ENST00000531673.5	c.*364-15747C>T		intron_variant, NMD_transcript_variant		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

Gnomad4 AFR AF: 0.598

Gnomad4 AMR AF: 0.763

Gnomad4 ASJ AF: 0.788

Gnomad4 EAS AF: 0.792

Gnomad4 SAS AF: 0.813

Gnomad4 FIN AF: 0.709

Gnomad4 NFE AF: 0.738

Gnomad4 OTH AF: 0.724

Alfa AF: 0.715 Hom.: 6141

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

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

Other links and lift over

dbSNP: rs2564871; hg19: chr11-112124533;