Variant chr11-36227087-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000315571.6(LDLRAD3):c.457C>T(p.Pro153Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000699 in 1,430,128 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

LDLRAD3
ENST00000315571.6 missense, splice_region

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.65

Variant links:

Genes affected

LDLRAD3 (HGNC:27046): (low density lipoprotein receptor class A domain containing 3) Predicted to enable amyloid-beta binding activity. Predicted to act upstream of or within receptor-mediated endocytosis and regulation of protein processing. Predicted to be located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

LDLRAD3 links:

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ACMG classification

Classification made for transcript

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=0.15704057).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
LDLRAD3	NM_174902.4 linkuse as main transcript	c.457C>T	p.Pro153Ser	missense_variant, splice_region_variant	5/6	ENST00000315571.6	NP_777562.1
LDLRAD3	NM_001304263.2 linkuse as main transcript	c.310C>T	p.Pro104Ser	missense_variant, splice_region_variant	4/5		NP_001291192.1
LDLRAD3	NM_001304264.2 linkuse as main transcript	c.94C>T	p.Pro32Ser	missense_variant, splice_region_variant	5/6		NP_001291193.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LDLRAD3	ENST00000315571.6 linkuse as main transcript	c.457C>T	p.Pro153Ser	missense_variant, splice_region_variant	5/6	1	NM_174902.4	ENSP00000318607	P1	Q86YD5-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.99e-7

AC:

AN:

1430128

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

706138

show subpopulations

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:

0.00

Gnomad4 OTH exome

AF:

0.0000170

GnomAD4 genome

Cov.:

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

Jan 18, 2023

The c.457C>T (p.P153S) alteration is located in exon 5 (coding exon 5) of the LDLRAD3 gene. This alteration results from a C to T substitution at nucleotide position 457, causing the proline (P) at amino acid position 153 to be replaced by a serine (S). 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

0.14

BayesDel_addAF

Uncertain

0.027

BayesDel_noAF

Benign

-0.20

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.026

.;.;T

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.12

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.79

T;T;T

M_CAP

Benign

0.062

MetaRNN

Benign

0.15

T;T;T

MetaSVM

Uncertain

0.057

MutationAssessor

Benign

0.69

.;.;N

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Benign

0.44

PROVEAN

Benign

-1.9

N;N;N

REVEL

Benign

0.17

Sift

Benign

0.13

T;T;T

Sift4G

Benign

0.45

T;T;T

Polyphen

1.0, 0.0020

.;D;B

Vest4

0.30

MutPred

0.41

.;.;Gain of relative solvent accessibility (P = 0.0166);

MVP

0.77

MPC

0.19

ClinPred

0.57

GERP RS

2.0

Varity_R

0.046

gMVP

0.47

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over