Variant 19-33205372-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002333.4(LRP3):c.602C>T(p.Ser201Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000688 in 1,598,944 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 (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000066 ( 0 hom. )

Consequence

LRP3
NM_002333.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.51

Variant links:

Genes affected

LRP3 (HGNC:6695): (LDL receptor related protein 3) Involved in negative regulation of fat cell differentiation; positive regulation of osteoblast differentiation; and regulation of gene expression. Predicted to be located in clathrin-coated pit. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

LRP3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19793361).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRP3	NM_002333.4 linkuse as main transcript	c.602C>T	p.Ser201Leu	missense_variant	5/7	ENST00000253193.9	NP_002324.2
LRP3	XM_005258945.2 linkuse as main transcript	c.602C>T	p.Ser201Leu	missense_variant	5/7		XP_005259002.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
LRP3	ENST00000253193.9 linkuse as main transcript	c.602C>T	p.Ser201Leu	missense_variant	5/7	1	NM_002333.4	ENSP00000253193	P1
LRP3	ENST00000590275.1 linkuse as main transcript	n.916C>T		non_coding_transcript_exon_variant	3/3	2
LRP3	ENST00000590278.1 linkuse as main transcript	n.1503C>T		non_coding_transcript_exon_variant	1/3	2

Frequencies

GnomAD3 genomes

AF:

0.0000920

AC:

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000143

AC:

AN:

231184

Hom.:

AF XY:

0.000118

AC XY:

AN XY:

127264

show subpopulations

Gnomad AFR exome

AF:

0.0000716

Gnomad AMR exome

AF:

0.000478

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000156

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000664

AC:

AN:

1446712

Hom.:

Cov.:

AF XY:

0.0000683

AC XY:

AN XY:

717286

show subpopulations

Gnomad4 AFR exome

AF:

0.0000903

Gnomad4 AMR exome

AF:

0.000386

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000196

Gnomad4 NFE exome

AF:

0.0000635

Gnomad4 OTH exome

AF:

0.0000839

GnomAD4 genome

AF:

0.0000920

AC:

AN:

152232

Hom.:

Cov.:

AF XY:

0.0000941

AC XY:

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000114

Hom.:

Bravo

AF:

0.0000831

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000915

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 16, 2024

The c.602C>T (p.S201L) alteration is located in exon 5 (coding exon 5) of the LRP3 gene. This alteration results from a C to T substitution at nucleotide position 602, causing the serine (S) at amino acid position 201 to be replaced by a leucine (L). 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

0.10

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.14

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.20

Eigen

Benign

0.030

Eigen_PC

Benign

0.049

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.87

M_CAP

Pathogenic

0.39

MetaRNN

Benign

0.20

MetaSVM

Uncertain

0.75

MutationAssessor

Uncertain

2.4

MutationTaster

Benign

0.80

D;D

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-1.3

REVEL

Benign

0.29

Sift

Benign

0.046

Sift4G

Benign

0.42

Polyphen

0.017

Vest4

0.18

MVP

0.89

MPC

0.38

ClinPred

0.064

GERP RS

4.0

Varity_R

0.12

gMVP

0.080

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