Variant 14-22872320-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_014045.5(LRP10):c.17T>G(p.Leu6Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000859 in 1,513,686 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000081 ( 0 hom. )

Consequence

LRP10
NM_014045.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.63

Variant links:

Genes affected

LRP10 (HGNC:14553): (LDL receptor related protein 10) This gene encodes a low density lipoprotein receptor family protein. A similar protein in mouse is thought to play a role in the uptake of apolipoprotein E-containing lipoproteins. [provided by RefSeq, Jul 2016]

LRP10 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.918

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
LRP10	NM_014045.5 linkuse as main transcript	c.17T>G	p.Leu6Arg	missense_variant	1/7	ENST00000359591.9	NP_054764.2
LRP10	NM_001329226.2 linkuse as main transcript	c.17T>G	p.Leu6Arg	missense_variant	1/8		NP_001316155.1
LRP10	XM_005267510.2 linkuse as main transcript	c.17T>G	p.Leu6Arg	missense_variant	1/7		XP_005267567.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRP10	ENST00000359591.9 linkuse as main transcript	c.17T>G	p.Leu6Arg	missense_variant	1/7	1	NM_014045.5	ENSP00000352601	P2	Q7Z4F1-1
LRP10	ENST00000546834.5 linkuse as main transcript	c.17T>G	p.Leu6Arg	missense_variant	1/8	5		ENSP00000447559	A2	Q7Z4F1-2

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151502

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000657

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

GnomAD3 exomes

AF:

0.00000848

AC:

AN:

235952

Hom.:

AF XY:

0.00000780

AC XY:

AN XY:

128206

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000614

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000808

AC:

AN:

1362070

Hom.:

Cov.:

AF XY:

0.0000103

AC XY:

AN XY:

679232

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:

0.00000773

Gnomad4 OTH exome

AF:

0.0000536

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151616

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74054

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000656

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:

0.00000756

ExAC

AF:

0.00000829

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

Jun 29, 2022

The c.17T>G (p.L6R) alteration is located in exon 1 (coding exon 1) of the LRP10 gene. This alteration results from a T to G substitution at nucleotide position 17, causing the leucine (L) at amino acid position 6 to be replaced by an arginine (R). 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

0.23

BayesDel_addAF

Uncertain

0.036

BayesDel_noAF

Uncertain

-0.010

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.027

T;.

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.26

FATHMM_MKL

Benign

0.47

LIST_S2

Benign

0.47

T;T

M_CAP

Pathogenic

0.46

MetaRNN

Pathogenic

0.92

D;D

MetaSVM

Uncertain

0.052

MutationAssessor

Benign

1.6

L;L

MutationTaster

Benign

0.98

N;N

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.93

N;N

REVEL

Uncertain

0.62

Sift

Uncertain

0.0080

D;D

Sift4G

Uncertain

0.011

D;D

Polyphen

0.70

P;.

Vest4

0.82

MutPred

0.77

Loss of stability (P = 0.0081);Loss of stability (P = 0.0081);

MVP

0.98

MPC

0.34

ClinPred

0.42

GERP RS

4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.27

gMVP

0.80

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