Variant chr19-33204795-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002333.4(LRP3):c.418C>T(p.His140Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000248 in 1,613,500 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

LRP3
NM_002333.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.98

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:

LRP3 (HGNC:):

LRP3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRP3	NM_002333.4 linkuse as main transcript	c.418C>T	p.His140Tyr	missense_variant	4/7	ENST00000253193.9	NP_002324.2	O75074
LRP3	XM_005258945.2 linkuse as main transcript	c.418C>T	p.His140Tyr	missense_variant	4/7		XP_005259002.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
LRP3	ENST00000253193.9 linkuse as main transcript	c.418C>T	p.His140Tyr	missense_variant	4/7	1	NM_002333.4	ENSP00000253193.6	O75074
LRP3	ENST00000592484.5 linkuse as main transcript	c.172C>T	p.His58Tyr	missense_variant	4/5	4		ENSP00000476735.1	V9GYG8
LRP3	ENST00000590275.1 linkuse as main transcript	n.339C>T		non_coding_transcript_exon_variant	3/3	2
LRP3	ENST00000590278.1 linkuse as main transcript	n.926C>T		non_coding_transcript_exon_variant	1/3	2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461294

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726996

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152206

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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 26, 2022

The c.418C>T (p.H140Y) alteration is located in exon 4 (coding exon 4) of the LRP3 gene. This alteration results from a C to T substitution at nucleotide position 418, causing the histidine (H) at amino acid position 140 to be replaced by a tyrosine (Y). 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

Pathogenic

0.62

BayesDel_addAF

Uncertain

0.027

BayesDel_noAF

Benign

-0.20

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.057

.;T

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.97

D;D

M_CAP

Benign

0.017

MetaRNN

Uncertain

0.65

D;D

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

.;L

PrimateAI

Uncertain

0.77

PROVEAN

Uncertain

-2.4

.;N

REVEL

Benign

0.23

Sift

Benign

0.13

.;T

Sift4G

Uncertain

0.011

D;T

Polyphen

1.0

.;D

Vest4

0.94

MutPred

0.61

.;Loss of disorder (P = 0.0733);

MVP

0.67

MPC

1.1

ClinPred

0.96

GERP RS

4.1

Varity_R

0.31

gMVP

0.60

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