3-188524777-G-A

Variant names:

• chr3-188524777-G-A
• rs200961679
• NM_001375462.1:c.419G>A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_001375462.1(LPP):​c.419G>A​(p.Arg140Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,613,414 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R140W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: LPP NM_001375462.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.60
• 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.320018).
• BS2: High AC in GnomAdExome4 at 21 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPP	NM_001375462.1	c.419G>A	p.Arg140Gln	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.419G>A	p.Arg140Gln	missense_variant	Exon 6 of 12	1	NM_001375462.1	ENSP00000478901.1

Frequencies

GnomAD3 genomes AF: 0.0000264 AC: 4 AN: 151782 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000657

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000239 AC: 6 AN: 250806 AF XY: 0.0000148

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000218

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000882

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000144 AC: 21 AN: 1461516 Hom.: 0 Cov.: 31 AF XY: 0.0000151 AC XY: 11 AN XY: 727062

African (AFR) AF: 0.0000299 AC: 1 AN: 33462

American (AMR) AF: 0.0000671 AC: 3 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26114

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39676

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00000810 AC: 9 AN: 1111788

Other (OTH) AF: 0.0000331 AC: 2 AN: 60380

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 151898 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74246

African (AFR) AF: 0.00 AC: 0 AN: 41422

American (AMR) AF: 0.0000656 AC: 1 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5162

South Asian (SAS) AF: 0.00 AC: 0 AN: 4798

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10552

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67950

Other (OTH) AF: 0.00 AC: 0 AN: 2108

Alfa AF: 0.0000249 Hom.: 0

ExAC AF: 0.0000330 AC: 4

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 15, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.419G>A (p.R140Q) alteration is located in exon 5 (coding exon 3) of the LPP gene. This alteration results from a G to A substitution at nucleotide position 419, causing the arginine (R) at amino acid position 140 to be replaced by a glutamine (Q). 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	0.14
BayesDel_addAF	Benign	-0.077	T
BayesDel_noAF	Uncertain	-0.060
CADD	Pathogenic	32
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.11	T;.;T;T;T
Eigen	Pathogenic	0.78
Eigen_PC	Pathogenic	0.78
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	D;D;D;.;D
M_CAP	Benign	0.084	D
MetaRNN	Benign	0.32	T;T;T;T;T
MetaSVM	Benign	-0.71	T
MutationAssessor	Benign	1.9	.;.;.;L;L
PhyloP100		9.6
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-2.8	D;D;.;.;.
REVEL	Benign	0.23
Sift	Uncertain	0.0060	D;D;.;.;.
Sift4G	Benign	0.36	T;T;T;.;T
Polyphen		1.0	D;.;.;D;D
Vest4		0.84
MVP		0.67
ClinPred		0.65	D
GERP RS		5.6
Varity_R		0.12
gMVP		0.53
Mutation Taster		=66/34	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: rs200961679; hg19: chr3-188242565;