Variant 6-149826344-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_032832.6(LRP11):c.1268G>A(p.Gly423Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000168 in 1,611,032 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

LRP11
NM_032832.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.77

Variant links:

Genes affected

LRP11 (HGNC:16936): (LDL receptor related protein 11) Enables phosphoprotein binding activity. Predicted to act upstream of or within several processes, including response to cold; response to immobilization stress; and response to water deprivation. Predicted to be located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

LRP11 links:

RAET1E-LRP11 (HGNC:):

RAET1E-LRP11 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=0.099436074).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRP11	NM_032832.6 linkuse as main transcript	c.1268G>A	p.Gly423Glu	missense_variant	6/7	ENST00000239367.7	NP_116221.3
RAET1E-LRP11	NR_182438.1 linkuse as main transcript	n.3168G>A		non_coding_transcript_exon_variant	14/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRP11	ENST00000239367.7 linkuse as main transcript	c.1268G>A	p.Gly423Glu	missense_variant	6/7	1	NM_032832.6	ENSP00000239367	P1	Q86VZ4-1
LRP11	ENST00000463728.1 linkuse as main transcript	n.131G>A		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000171

AC:

AN:

1458920

Hom.:

Cov.:

AF XY:

0.0000152

AC XY:

AN XY:

725942

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000207

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152112

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.0000483

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:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000113

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

Nov 08, 2022

The c.1268G>A (p.G423E) alteration is located in exon 6 (coding exon 6) of the LRP11 gene. This alteration results from a G to A substitution at nucleotide position 1268, causing the glycine (G) at amino acid position 423 to be replaced by a glutamic acid (E). 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

0.084

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.0035

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.21

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.72

M_CAP

Benign

0.019

MetaRNN

Benign

0.099

MetaSVM

Uncertain

-0.062

MutationAssessor

Uncertain

2.5

MutationTaster

Benign

0.68

D;D

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.5

REVEL

Benign

0.075

Sift

Uncertain

0.022

Sift4G

Benign

0.17

Polyphen

0.31

Vest4

0.18

MutPred

0.090

Loss of glycosylation at S422 (P = 0.0566);

MVP

0.36

MPC

0.40

ClinPred

0.74

GERP RS

3.9

Varity_R

0.12

gMVP

0.27

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