dbSNP rs7645635: LPP:p.Tyr346His (chr3-188609767-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001375462.1(LPP):c.1036T>C(p.Tyr346His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0339 in 1,613,912 control chromosomes in the GnomAD database, including 14,298 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.17 ( 7521 hom., cov: 32)

Exomes 𝑓: 0.019 ( 6777 hom. )

Consequence

LPP
NM_001375462.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 7.23

Variant links:

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]

LPP links:

LOC124906316 (HGNC:):

LOC124906316 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=7.5052405E-5).

BP6

Variant 3-188609767-T-C is Benign according to our data. Variant chr3-188609767-T-C is described in ClinVar as [Benign]. Clinvar id is 1256811.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.591 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPP	NM_001375462.1 link	c.1036T>C	p.Tyr346His	missense_variant	Exon 7 of 12	ENST00000617246.5	NP_001362391.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPP	ENST00000617246.5 link	c.1036T>C	p.Tyr346His	missense_variant	Exon 7 of 12	1	NM_001375462.1	ENSP00000478901.1		Q93052

Frequencies

GnomAD3 genomes

AF:

0.174

AC:

26387

AN:

151982

Hom.:

7500

Cov.:

show subpopulations

Gnomad AFR

AF:

0.598

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0749

Gnomad ASJ

AF:

0.00922

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00352

Gnomad FIN

AF:

0.000941

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.00350

Gnomad OTH

AF:

0.126

GnomAD3 exomes

AF:

0.0469

AC:

11685

AN:

249002

Hom.:

3069

AF XY:

0.0351

AC XY:

4736

AN XY:

134970

show subpopulations

Gnomad AFR exome

AF:

0.616

Gnomad AMR exome

AF:

0.0336

Gnomad ASJ exome

AF:

0.0100

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00350

Gnomad FIN exome

AF:

0.00111

Gnomad NFE exome

AF:

0.00322

Gnomad OTH exome

AF:

0.0220

GnomAD4 exome

AF:

0.0193

AC:

28261

AN:

1461812

Hom.:

6777

Cov.:

AF XY:

0.0169

AC XY:

12301

AN XY:

727202

show subpopulations

Gnomad4 AFR exome

AF:

0.616

Gnomad4 AMR exome

AF:

0.0377

Gnomad4 ASJ exome

AF:

0.0111

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00399

Gnomad4 FIN exome

AF:

0.00103

Gnomad4 NFE exome

AF:

0.00223

Gnomad4 OTH exome

AF:

0.0416

GnomAD4 genome

AF:

0.174

AC:

26449

AN:

152100

Hom.:

7521

Cov.:

AF XY:

0.166

AC XY:

12384

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.597

Gnomad4 AMR

AF:

0.0748

Gnomad4 ASJ

AF:

0.00922

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00249

Gnomad4 FIN

AF:

0.000941

Gnomad4 NFE

AF:

0.00350

Gnomad4 OTH

AF:

0.125

Alfa

AF:

0.0396

Hom.:

2513

Bravo

AF:

0.199

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.00363

AC:

ESP6500AA

AF:

0.586

AC:

2581

ESP6500EA

AF:

0.00395

AC:

ExAC

AF:

0.0568

AC:

6900

Asia WGS

AF:

0.0360

AC:

125

AN:

3478

EpiCase

AF:

0.00414

EpiControl

AF:

0.00528

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 09, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.17

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

T;T;T;T;T

Eigen

Uncertain

0.50

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Benign

0.80

T;T;.;T;T

MetaRNN

Benign

0.000075

T;T;T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Uncertain

2.2

.;.;M;M;.

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-1.2

N;.;.;.;N

REVEL

Benign

0.21

Sift

Uncertain

0.0050

D;.;.;.;D

Sift4G

Benign

0.41

T;T;.;T;T

Polyphen

1.0

D;.;D;D;.

Vest4

0.85

ClinPred

0.038

GERP RS

6.2

Varity_R

0.081

gMVP

0.55

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over