chr11-112260564-A-G

Position:

• chr11-112260564-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001145024.1(PLET1):​c.26T>C​(p.Leu9Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PLET1 NM_001145024.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.25

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]

ENSG00000268472 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38597542).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLET1	NM_001145024.1	c.26T>C	p.Leu9Pro	missense_variant	1/4	ENST00000338832.4	NP_001138496.1
LOC100132686	NR_133566.1	n.300A>G		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLET1	ENST00000338832.4	c.26T>C	p.Leu9Pro	missense_variant	1/4	5	NM_001145024.1	ENSP00000341412.2
PTS	ENST00000531673.5	n.*364-8993A>G		intron_variant		1		ENSP00000433469.1
ENSG00000268472	ENST00000595053.2	n.300A>G		non_coding_transcript_exon_variant	1/1	6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 03, 2021

The c.26T>C (p.L9P) alteration is located in exon 1 (coding exon 1) of the PLET1 gene. This alteration results from a T to C substitution at nucleotide position 26, causing the leucine (L) at amino acid position 9 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Uncertain	0.028	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.025	T
Eigen	Benign	-0.011
Eigen_PC	Benign	-0.11
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.27	T
M_CAP	Benign	0.072	D
MetaRNN	Benign	0.39	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	0.46	N
PROVEAN	Benign	-0.64	N
REVEL	Uncertain	0.30
Sift	Benign	0.13	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.99	D
Vest4		0.38
MutPred		0.50		Loss of helix (P = 0.0237);
MVP		0.66
ClinPred		0.55	D
GERP RS		3.7
Varity_R		0.14
gMVP		0.67

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-112131287;