Variant 14-22875213-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_014045.5(LRP10):c.374T>C(p.Met125Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000174 in 1,607,812 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

LRP10
NM_014045.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.609

Variant links:

Genes affected

LRP10 (HGNC:14553): (LDL receptor related protein 10) This gene encodes a low density lipoprotein receptor family protein. A similar protein in mouse is thought to play a role in the uptake of apolipoprotein E-containing lipoproteins. [provided by RefSeq, Jul 2016]

LRP10 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06331086).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRP10	NM_014045.5 link	c.374T>C	p.Met125Thr	missense_variant	4/7	ENST00000359591.9	NP_054764.2	Q7Z4F1-1
LRP10	NM_001329226.2 link	c.374T>C	p.Met125Thr	missense_variant	4/8		NP_001316155.1	Q7Z4F1-2
LRP10	XM_005267510.2 link	c.374T>C	p.Met125Thr	missense_variant	4/7		XP_005267567.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
LRP10	ENST00000359591.9 link	c.374T>C	p.Met125Thr	missense_variant	4/7	1	NM_014045.5	ENSP00000352601.4	Q7Z4F1-1
LRP10	ENST00000551466.1 link	c.77T>C	p.Met26Thr	missense_variant	1/5	1		ENSP00000447977.1	H0YHW7
LRP10	ENST00000546834.5 link	c.374T>C	p.Met125Thr	missense_variant	4/8	5		ENSP00000447559.1	Q7Z4F1-2
LRP10	ENST00000553002.1 link	n.521T>C		non_coding_transcript_exon_variant	2/3	2

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000204

AC:

AN:

244808

Hom.:

AF XY:

0.00000756

AC XY:

AN XY:

132242

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000453

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000137

AC:

AN:

1455676

Hom.:

Cov.:

AF XY:

0.0000111

AC XY:

AN XY:

723608

show subpopulations

Gnomad4 AFR exome

AF:

0.0000599

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:

0.0000153

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152136

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000136

Hom.:

Bravo

AF:

0.0000491

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 14, 2021

The c.374T>C (p.M125T) alteration is located in exon 4 (coding exon 4) of the LRP10 gene. This alteration results from a T to C substitution at nucleotide position 374, causing the methionine (M) at amino acid position 125 to be replaced by a threonine (T). 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

0.084

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.51

DEOGEN2

Benign

0.012

T;.

Eigen

Benign

-0.96

Eigen_PC

Benign

-0.77

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.30

T;T

M_CAP

Benign

0.0050

MetaRNN

Benign

0.063

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

L;L

PrimateAI

Benign

0.46

PROVEAN

Benign

0.10

N;N

REVEL

Benign

0.032

Sift

Benign

0.45

T;T

Sift4G

Benign

0.64

T;T

Polyphen

0.0

B;.

Vest4

0.28

MVP

0.12

MPC

0.27

ClinPred

0.025

GERP RS

1.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.029

gMVP

0.34

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over