chr6-149843052-C-G

Position:

• chr6-149843052-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The ENST00000239367.7(LRP11):​c.844G>C​(p.Asp282His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LRP11 ENST00000239367.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.16

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]

ENSG00000285991 (HGNC:):

ACMG classification

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, 0.91

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRP11	NM_032832.6	c.844G>C	p.Asp282His	missense_variant	3/7	ENST00000239367.7	NP_116221.3
LRP11	NM_001410946.1	c.844G>C	p.Asp282His	missense_variant	3/4		NP_001397875.1
RAET1E-LRP11	NR_182438.1	n.2744G>C		non_coding_transcript_exon_variant	11/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRP11	ENST00000239367.7	c.844G>C	p.Asp282His	missense_variant	3/7	1	NM_032832.6	ENSP00000239367.2
ENSG00000285991	ENST00000647612.1	n.*730G>C		non_coding_transcript_exon_variant	11/15			ENSP00000498179.1
ENSG00000285991	ENST00000647612.1	n.*730G>C		3_prime_UTR_variant	11/15			ENSP00000498179.1
LRP11	ENST00000367368.3	c.844G>C	p.Asp282His	missense_variant	3/4	2		ENSP00000356338.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 14, 2021

The c.844G>C (p.D282H) alteration is located in exon 3 (coding exon 3) of the LRP11 gene. This alteration results from a G to C substitution at nucleotide position 844, causing the aspartic acid (D) at amino acid position 282 to be replaced by a histidine (H). 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	0.98
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.11
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.34	T;D
Eigen	Pathogenic	0.73
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.95	D;D
M_CAP	Benign	0.065	D
MetaRNN	Pathogenic	0.91	D;D
MetaSVM	Benign	-0.54	T
MutationAssessor	Pathogenic	3.3	M;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.59	T
PROVEAN	Pathogenic	-6.0	D;D
REVEL	Uncertain	0.44
Sift	Uncertain	0.0050	D;D
Sift4G	Uncertain	0.0060	D;D
Polyphen		1.0	D;D
Vest4		0.95
MutPred		0.60		Loss of loop (P = 0.1242);Loss of loop (P = 0.1242);
MVP		0.82
MPC		1.1
ClinPred		1.0	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.58
gMVP		0.85

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.

Other links and lift over

hg19: chr6-150164188;