3-188524971-CTTTTTT-CTTTT

Variant names:

• chr3-188524971-CTT-C
• rs540192956
• NM_001375462.1:c.429+198_429+199delTT

Variant summary

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

The NM_001375462.1(LPP):​c.429+198_429+199delTT variant causes a intron change involving the alteration of a non-conserved nucleotide. There is a variant allele frequency bias in the population database for this variant (GnomAd4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.000042 (0 hom., cov: 0)
• Consequence: LPP NM_001375462.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28
• 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.

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.429+198_429+199delTT		intron	N/A	NP_001362391.1	Q93052
	LPP	NM_001167671.3		c.429+198_429+199delTT		intron	N/A	NP_001161143.1	Q93052
	LPP	NM_001375455.1		c.429+198_429+199delTT		intron	N/A	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.429+185_429+186delTT		intron	N/A	ENSP00000478901.1	Q93052
	LPP	ENST00000618621.5	TSL:1	c.429+185_429+186delTT		intron	N/A	ENSP00000482617.2	Q93052
	LPP	ENST00000414139.6	TSL:4	c.429+185_429+186delTT		intron	N/A	ENSP00000392667.2	Q93052

Frequencies

GnomAD3 genomes AF: 0.0000419 AC: 5 AN: 119332 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000916

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000228

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000505

Gnomad OTH AF: 0.00

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0000419 AC: 5 AN: 119332 Hom.: 0 Cov.: 0 AF XY: 0.0000902 AC XY: 5 AN XY: 55424

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 30888

American (AMR) AF: 0.0000916 AC: 1 AN: 10920

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3098

East Asian (EAS) AF: 0.00 AC: 0 AN: 4222

South Asian (SAS) AF: 0.00 AC: 0 AN: 3738

European-Finnish (FIN) AF: 0.000228 AC: 1 AN: 4378

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 252

European-Non Finnish (NFE) AF: 0.0000505 AC: 3 AN: 59438

Other (OTH) AF: 0.00 AC: 0 AN: 1580

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.3
Mutation Taster		=100/0	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: rs540192956; hg19: chr3-188242759;