8-104495159-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_013437.5(LRP12):​c.1631A>G​(p.Glu544Gly) variant causes a missense change involving the alteration of a conserved nucleotide. 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

LRP12
NM_013437.5 missense

Scores

11
7
1

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.01
Variant links:
Genes affected
LRP12 (HGNC:31708): (LDL receptor related protein 12) This gene encodes a member of the low-density lipoprotein receptor related protein family. The product of this gene is a transmembrane protein that is differentially expressed in many cancer cells. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Feb 2010]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.78

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
LRP12NM_013437.5 linkuse as main transcriptc.1631A>G p.Glu544Gly missense_variant 6/7 ENST00000276654.10 NP_038465.1 Q9Y561-1Q59H02
LRP12NM_001135703.3 linkuse as main transcriptc.1574A>G p.Glu525Gly missense_variant 5/6 NP_001129175.1 Q9Y561-2Q59H02

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
LRP12ENST00000276654.10 linkuse as main transcriptc.1631A>G p.Glu544Gly missense_variant 6/71 NM_013437.5 ENSP00000276654.5 Q9Y561-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsFeb 21, 2024The c.1631A>G (p.E544G) alteration is located in exon 6 (coding exon 6) of the LRP12 gene. This alteration results from a A to G substitution at nucleotide position 1631, causing the glutamic acid (E) at amino acid position 544 to be replaced by a glycine (G). 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
0.91
BayesDel_addAF
Pathogenic
0.50
D
BayesDel_noAF
Pathogenic
0.49
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.50
.;T;T
Eigen
Pathogenic
0.74
Eigen_PC
Pathogenic
0.76
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Pathogenic
0.99
D;D;D
M_CAP
Pathogenic
0.41
D
MetaRNN
Pathogenic
0.78
D;D;D
MetaSVM
Pathogenic
0.94
D
MutationAssessor
Uncertain
2.1
.;M;.
PrimateAI
Uncertain
0.72
T
PROVEAN
Uncertain
-3.7
D;D;D
REVEL
Pathogenic
0.72
Sift
Uncertain
0.0010
D;D;D
Sift4G
Uncertain
0.0060
D;D;.
Polyphen
1.0
D;D;.
Vest4
0.74
MutPred
0.28
.;Loss of stability (P = 0.06);.;
MVP
0.90
MPC
0.47
ClinPred
0.99
D
GERP RS
5.7
Varity_R
0.43
gMVP
0.59

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: chr8-105507387; API