NM_001375462.1:c.299A>C

Variant names:

• chr3-188484697-A-C
• rs768685184
• NM_001375462.1:c.299A>C

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.299A>C​(p.Lys100Thr) 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. 15/22 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: 1.67
• 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=0.096954346).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001375462.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPP	NM_001375462.1	MANE Select	c.299A>C	p.Lys100Thr	missense	Exon 5 of 12	NP_001362391.1	Q93052
	LPP	NM_001167671.3		c.299A>C	p.Lys100Thr	missense	Exon 5 of 12	NP_001161143.1	Q93052
	LPP	NM_001375455.1		c.299A>C	p.Lys100Thr	missense	Exon 4 of 11	NP_001362384.1	Q93052

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPP	ENST00000617246.5	TSL:1 MANE Select	c.299A>C	p.Lys100Thr	missense	Exon 5 of 12	ENSP00000478901.1	Q93052
	LPP	ENST00000618621.5	TSL:1	c.299A>C	p.Lys100Thr	missense	Exon 4 of 11	ENSP00000482617.2	Q93052
	LPP	ENST00000414139.6	TSL:4	c.299A>C	p.Lys100Thr	missense	Exon 4 of 11	ENSP00000392667.2	Q93052

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.14
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.097	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.69	N
PhyloP100		1.7
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.72	N
REVEL	Benign	0.055
Sift	Benign	0.31	T
Sift4G	Benign	0.50	T
Polyphen		0.15	B
Vest4		0.28
MutPred		0.36		Loss of methylation at K100 (P = 6e-04)
MVP		0.23
ClinPred		0.32	T
GERP RS		3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.050
gMVP		0.21
Mutation Taster		=95/5	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

dbSNP: rs768685184; hg19: chr3-188202485;