Variant 6-149863935-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_032832.6(LRP11):c.86G>A(p.Cys29Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

LRP11
NM_032832.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.43

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-AS1 (HGNC:48994): (RAET1E antisense RNA 1)

RAET1E-AS1 links:

RAET1E-LRP11 (HGNC:):

RAET1E-LRP11 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.28145975).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
LRP11	NM_032832.6 linkuse as main transcript	c.86G>A	p.Cys29Tyr	missense_variant	1/7	ENST00000239367.7	NP_116221.3
RAET1E-AS1	NR_045126.1 linkuse as main transcript	n.438C>T		non_coding_transcript_exon_variant	1/2
RAET1E-LRP11	NR_182438.1 linkuse as main transcript	n.2513+950G>A		intron_variant, non_coding_transcript_variant
LRP11	NM_001410946.1 linkuse as main transcript	c.86G>A	p.Cys29Tyr	missense_variant	1/4		NP_001397875.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRP11	ENST00000239367.7 linkuse as main transcript	c.86G>A	p.Cys29Tyr	missense_variant	1/7	1	NM_032832.6	ENSP00000239367	P1	Q86VZ4-1
RAET1E-AS1	ENST00000606915.1 linkuse as main transcript	n.442C>T		non_coding_transcript_exon_variant	1/2	1
LRP11	ENST00000367368.3 linkuse as main transcript	c.86G>A	p.Cys29Tyr	missense_variant	1/4	2		ENSP00000356338

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1322392

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

651952

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Apr 13, 2023

The c.86G>A (p.C29Y) alteration is located in exon 1 (coding exon 1) of the LRP11 gene. This alteration results from a G to A substitution at nucleotide position 86, causing the cysteine (C) at amino acid position 29 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

Uncertain

0.40

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.016

T;T

Eigen

Benign

-0.022

Eigen_PC

Benign

-0.049

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.54

T;T

M_CAP

Uncertain

0.26

MetaRNN

Benign

0.28

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

2.0

M;.

MutationTaster

Benign

1.0

D;N;N

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-1.4

N;N

REVEL

Benign

0.065

Sift

Pathogenic

0.0

D;D

Sift4G

Uncertain

0.037

D;D

Polyphen

0.95

P;P

Vest4

0.22

MutPred

0.58

Loss of disorder (P = 0.0542);Loss of disorder (P = 0.0542);

MVP

0.43

MPC

2.3

ClinPred

0.97

GERP RS

3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.57

gMVP

0.34

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over