chr3-188524782-C-T

Variant names:

• chr3-188524782-C-T
• NM_001375462.1:c.424C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001375462.1(LPP):​c.424C>T​(p.Pro142Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LPP NM_001375462.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.66
• Publications: 0 publications found

Genes affected

LPP (HGNC:6679): (LIM domain containing preferred translocation partner in lipoma) This gene encodes a member of a subfamily of LIM domain proteins that are characterized by an N-terminal proline-rich region and three C-terminal LIM domains. The encoded protein localizes to the cell periphery in focal adhesions and may be involved in cell-cell adhesion and cell motility. This protein also shuttles through the nucleus and may function as a transcriptional co-activator. This gene is located at the junction of certain disease-related chromosomal translocations, which result in the expression of chimeric proteins that may promote tumor growth. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19334012).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPP	NM_001375462.1	c.424C>T	p.Pro142Ser	missense_variant	Exon 6 of 12	ENST00000617246.5	NP_001362391.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPP	ENST00000617246.5	c.424C>T	p.Pro142Ser	missense_variant	Exon 6 of 12	1	NM_001375462.1	ENSP00000478901.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 07, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.424C>T (p.P142S) alteration is located in exon 5 (coding exon 3) of the LPP gene. This alteration results from a C to T substitution at nucleotide position 424, causing the proline (P) at amino acid position 142 to be replaced by a serine (S). 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	0.058
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	16
DANN	Uncertain	1.0
DEOGEN2	Benign	0.059	T;.;T;T;T
Eigen	Benign	-0.046
Eigen_PC	Benign	0.034
FATHMM_MKL	Benign	0.39	N
LIST_S2	Benign	0.79	T;T;T;.;T
M_CAP	Benign	0.0076	T
MetaRNN	Benign	0.19	T;T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.2	.;.;.;L;L
PhyloP100		3.7
PrimateAI	Benign	0.33	T
PROVEAN	Uncertain	-2.9	D;D;.;.;.
REVEL	Benign	0.063
Sift	Benign	0.20	T;T;.;.;.
Sift4G	Benign	0.089	T;T;T;.;T
Polyphen		0.73	P;.;.;B;B
Vest4		0.33
MutPred		0.25		Gain of phosphorylation at P142 (P = 0.0027);Gain of phosphorylation at P142 (P = 0.0027);.;Gain of phosphorylation at P142 (P = 0.0027);Gain of phosphorylation at P142 (P = 0.0027);
MVP		0.29
ClinPred		0.63	D
GERP RS		5.6
Varity_R		0.052
gMVP		0.24
Mutation Taster		=90/10	polymorphism

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

hg19: chr3-188242570;