3-188524909-T-G

Position:

• chr3-188524909-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001375462.1(LPP):​c.429+122T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.35 (8493 hom., cov: 20)
  • Exomes 𝑓: 0.29 (15344 hom.)
  • Failed GnomAD Quality Control
• Consequence: LPP NM_001375462.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.215

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

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 3-188524909-T-G is Benign according to our data. Variant chr3-188524909-T-G is described in ClinVar as [Benign]. Clinvar id is 1271654.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.395 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LPP	NM_001375462.1	c.429+122T>G		intron_variant		ENST00000617246.5	NP_001362391.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LPP	ENST00000617246.5	c.429+122T>G		intron_variant		1	NM_001375462.1	ENSP00000478901.1

Frequencies

GnomAD3 genomes AF: 0.351 AC: 46483 AN: 132488 Hom.: 8493 Cov.: 20

Gnomad AFR AF: 0.401

Gnomad AMI AF: 0.426

Gnomad AMR AF: 0.312

Gnomad ASJ AF: 0.353

Gnomad EAS AF: 0.0332

Gnomad SAS AF: 0.308

Gnomad FIN AF: 0.333

Gnomad MID AF: 0.401

Gnomad NFE AF: 0.358

Gnomad OTH AF: 0.366

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.286 AC: 95580 AN: 334708 Hom.: 15344 AF XY: 0.287 AC XY: 50410 AN XY: 175602

Gnomad4 AFR exome AF: 0.391

Gnomad4 AMR exome AF: 0.217

Gnomad4 ASJ exome AF: 0.326

Gnomad4 EAS exome AF: 0.0426

Gnomad4 SAS exome AF: 0.272

Gnomad4 FIN exome AF: 0.348

Gnomad4 NFE exome AF: 0.304

Gnomad4 OTH exome AF: 0.305

GnomAD4 genome AF: 0.351 AC: 46508 AN: 132536 Hom.: 8493 Cov.: 20 AF XY: 0.344 AC XY: 21833 AN XY: 63462

Gnomad4 AFR AF: 0.401

Gnomad4 AMR AF: 0.312

Gnomad4 ASJ AF: 0.353

Gnomad4 EAS AF: 0.0331

Gnomad4 SAS AF: 0.309

Gnomad4 FIN AF: 0.333

Gnomad4 NFE AF: 0.358

Gnomad4 OTH AF: 0.367

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.7
DANN	Benign	0.42

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

LitVar

Other links and lift over

dbSNP: rs369579197; hg19: chr3-188242697;