rs769678128

Variant names:

• chr8-104491533-C-G
• NM_013437.5:c.1720G>C

Your query was ambiguous. Multiple possible variants found:

• chr8-104491533-C-G
• chr8-104491533-C-T

Variant summary

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

The NM_013437.5(LRP12):​c.1720G>C​(p.Val574Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,443,810 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V574I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: LRP12 NM_013437.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.35

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRP12	NM_013437.5	c.1720G>C	p.Val574Leu	missense_variant	Exon 7 of 7	ENST00000276654.10	NP_038465.1
LRP12	NM_001135703.3	c.1663G>C	p.Val555Leu	missense_variant	Exon 6 of 6		NP_001129175.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRP12	ENST00000276654.10	c.1720G>C	p.Val574Leu	missense_variant	Exon 7 of 7	1	NM_013437.5	ENSP00000276654.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1443810 Hom.: 0 Cov.: 32 AF XY: 0.00000139 AC XY: 1 AN XY: 717952

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: 0.00000181

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.53
BayesDel_addAF	Pathogenic	0.34	D
BayesDel_noAF	Pathogenic	0.25
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	.;T;T
Eigen	Pathogenic	0.73
Eigen_PC	Pathogenic	0.77
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.89	D;D;D
M_CAP	Uncertain	0.20	D
MetaRNN	Uncertain	0.71	D;D;D
MetaSVM	Pathogenic	0.85	D
MutationAssessor	Benign	2.0	.;M;.
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-0.92	N;N;N
REVEL	Uncertain	0.64
Sift	Uncertain	0.0090	D;D;D
Sift4G	Benign	0.078	T;T;.
Polyphen		0.99	D;D;.
Vest4		0.71
MutPred		0.41		.;Loss of catalytic residue at V574 (P = 0.0541);.;
MVP		0.83
MPC		0.71
ClinPred		0.79	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.25
gMVP		0.70

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: chr8-105503761;