8-104491533-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_013437.5(LRP12):​c.1720G>A​(p.Val574Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000762 in 1,443,810 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000076 ( 0 hom. )

Consequence

LRP12
NM_013437.5 missense

Scores

5
6
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.35
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.4046406).
BS2
High AC in GnomAdExome4 at 11 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LRP12NM_013437.5 linkc.1720G>A p.Val574Ile missense_variant Exon 7 of 7 ENST00000276654.10 NP_038465.1 Q9Y561-1Q59H02
LRP12NM_001135703.3 linkc.1663G>A p.Val555Ile missense_variant Exon 6 of 6 NP_001129175.1 Q9Y561-2Q59H02

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LRP12ENST00000276654.10 linkc.1720G>A p.Val574Ile missense_variant Exon 7 of 7 1 NM_013437.5 ENSP00000276654.5 Q9Y561-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000299
AC:
7
AN:
233754
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
127124
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000222
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000762
AC:
11
AN:
1443810
Hom.:
0
Cov.:
32
AF XY:
0.00000418
AC XY:
3
AN XY:
717952
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000196
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:
0.00000271
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378
ExAC
AF:
0.00000824
AC:
1

ClinVar

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

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Aug 30, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1720G>A (p.V574I) alteration is located in exon 7 (coding exon 7) of the LRP12 gene. This alteration results from a G to A substitution at nucleotide position 1720, causing the valine (V) at amino acid position 574 to be replaced by an isoleucine (I). 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
0.11
BayesDel_addAF
Benign
-0.0072
T
BayesDel_noAF
Uncertain
0.030
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.24
.;T;T
Eigen
Pathogenic
0.73
Eigen_PC
Pathogenic
0.77
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.90
D;D;D
M_CAP
Uncertain
0.11
D
MetaRNN
Benign
0.40
T;T;T
MetaSVM
Pathogenic
0.84
D
MutationAssessor
Benign
2.0
.;M;.
PrimateAI
Pathogenic
0.81
D
PROVEAN
Benign
-0.38
N;N;N
REVEL
Uncertain
0.49
Sift
Uncertain
0.011
D;D;D
Sift4G
Benign
0.093
T;T;.
Polyphen
0.99
D;D;.
Vest4
0.50
MutPred
0.35
.;Loss of catalytic residue at V574 (P = 0.0215);.;
MVP
0.65
MPC
0.68
ClinPred
0.48
T
GERP RS
5.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.12
gMVP
0.53

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.

Other links and lift over

dbSNP: rs769678128; hg19: chr8-105503761; API