Variant 11-36098353-G-A 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_174902.4(LDLRAD3):c.346G>A(p.Ala116Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000039 in 1,614,120 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: 𝑓 0.000072 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000036 ( 0 hom. )

Consequence

LDLRAD3
NM_174902.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.65

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:

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=0.02145201).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
LDLRAD3	NM_174902.4 linkuse as main transcript	c.346G>A	p.Ala116Thr	missense_variant	4/6	ENST00000315571.6	NP_777562.1
LDLRAD3	NM_001304263.2 linkuse as main transcript	c.199G>A	p.Ala67Thr	missense_variant	3/5		NP_001291192.1
LDLRAD3	NM_001304264.2 linkuse as main transcript	c.-134G>A		5_prime_UTR_variant	3/6		NP_001291193.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LDLRAD3	ENST00000315571.6 linkuse as main transcript	c.346G>A	p.Ala116Thr	missense_variant	4/6	1	NM_174902.4	ENSP00000318607	P1	Q86YD5-1
LDLRAD3	ENST00000528989.5 linkuse as main transcript	c.199G>A	p.Ala67Thr	missense_variant	3/5	1		ENSP00000433954		Q86YD5-2
LDLRAD3	ENST00000524419.5 linkuse as main transcript	c.199G>A	p.Ala67Thr	missense_variant	3/6	5		ENSP00000434313
LDLRAD3	ENST00000532490.1 linkuse as main transcript	n.300G>A		non_coding_transcript_exon_variant	4/5	4

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00154

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000152

AC:

AN:

250416

Hom.:

AF XY:

0.000155

AC XY:

AN XY:

135388

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00185

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000266

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000356

AC:

AN:

1461804

Hom.:

Cov.:

AF XY:

0.0000358

AC XY:

AN XY:

727208

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000982

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000108

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000722

AC:

AN:

152316

Hom.:

Cov.:

AF XY:

0.0000805

AC XY:

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00154

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000378

ExAC

AF:

0.000148

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

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

Dec 21, 2023

The c.346G>A (p.A116T) alteration is located in exon 4 (coding exon 4) of the LDLRAD3 gene. This alteration results from a G to A substitution at nucleotide position 346, causing the alanine (A) at amino acid position 116 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

0.092

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Uncertain

-0.050

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.087

.;.;T

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.029

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.64

T;T;T

M_CAP

Benign

0.041

MetaRNN

Benign

0.021

T;T;T

MetaSVM

Uncertain

0.10

MutationAssessor

Benign

-1.1

.;.;N

MutationTaster

Benign

0.85

D;D;D

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-0.92

N;N;N

REVEL

Uncertain

0.31

Sift

Benign

0.16

T;T;T

Sift4G

Benign

0.66

T;T;T

Polyphen

0.26

.;.;B

Vest4

0.32

MutPred

0.52

.;.;Gain of glycosylation at A116 (P = 0.0286);

MVP

0.80

MPC

0.18

ClinPred

0.044

GERP RS

5.0

Varity_R

0.056

gMVP

0.44

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