chr19-33205272-G-C

Position:

• chr19-33205272-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002333.4(LRP3):​c.502G>C​(p.Ala168Pro) 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. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: LRP3 NM_002333.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.412

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 (HGNC:):

ACMG classification

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=0.11752123).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRP3	NM_002333.4	c.502G>C	p.Ala168Pro	missense_variant	5/7	ENST00000253193.9	NP_002324.2
LRP3	XM_005258945.2	c.502G>C	p.Ala168Pro	missense_variant	5/7		XP_005259002.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRP3	ENST00000253193.9	c.502G>C	p.Ala168Pro	missense_variant	5/7	1	NM_002333.4	ENSP00000253193.6
LRP3	ENST00000592484.5	c.256G>C	p.Ala86Pro	missense_variant	5/5	4		ENSP00000476735.1
LRP3	ENST00000590275.1	n.816G>C		non_coding_transcript_exon_variant	3/3	2
LRP3	ENST00000590278.1	n.1403G>C		non_coding_transcript_exon_variant	1/3	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

Oct 06, 2024

The c.502G>C (p.A168P) alteration is located in exon 5 (coding exon 5) of the LRP3 gene. This alteration results from a G to C substitution at nucleotide position 502, causing the alanine (A) at amino acid position 168 to be replaced by a proline (P). 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	0.067
BayesDel_addAF	Benign	-0.035	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	16
DANN	Benign	0.87
DEOGEN2	Benign	0.11	.;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.078	N
LIST_S2	Benign	0.15	T;T
M_CAP	Benign	0.079	D
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-0.50	T
MutationAssessor	Benign	-0.30	.;N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.13	.;N
REVEL	Benign	0.29
Sift	Benign	0.43	.;T
Sift4G	Benign	0.26	T;T
Polyphen		0.0060	.;B
Vest4		0.15
MutPred		0.53		.;Gain of disorder (P = 0.0497);
MVP		0.66
MPC		0.55
ClinPred		0.084	T
GERP RS		-1.4
Varity_R		0.065
gMVP		0.42

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: chr19-33696178;