Genetic Variant LDLRAD3:p.Ala46Ser (chr11-36036192-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_174902.4(LDLRAD3):c.136G>T(p.Ala46Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000752 in 1,461,858 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. 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. A46T) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

LDLRAD3
NM_174902.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.16

Publications

7 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15672976).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_174902.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LDLRAD3	NM_174902.4	MANE Select	c.136G>T	p.Ala46Ser	missense	Exon 2 of 6	NP_777562.1	Q86YD5-1
LDLRAD3	NM_001304263.2		c.47-45461G>T		intron	N/A	NP_001291192.1	Q86YD5-2
LDLRAD3	NM_001304264.2		c.-286-45461G>T		intron	N/A	NP_001291193.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LDLRAD3	ENST00000315571.6	TSL:1 MANE Select	c.136G>T	p.Ala46Ser	missense	Exon 2 of 6	ENSP00000318607.5	Q86YD5-1
LDLRAD3	ENST00000528989.5	TSL:1	c.47-45461G>T		intron	N/A	ENSP00000433954.1	Q86YD5-2
LDLRAD3	ENST00000872891.1		c.136G>T	p.Ala46Ser	missense	Exon 2 of 6	ENSP00000542950.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000796

AC:

AN:

251348

AF XY:

0.00000736

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

0.00000752

AC:

AN:

1461858

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727238

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.0000447

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53390

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000809

AC:

AN:

1112006

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.448

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.23

CADD

Benign

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.080

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.56

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.69

M_CAP

Benign

0.043

MetaRNN

Benign

0.16

MetaSVM

Benign

-0.54

MutationAssessor

Benign

-0.010

PhyloP100

5.2

PrimateAI

Benign

0.37

PROVEAN

Benign

0.020

REVEL

Benign

0.24

Sift

Benign

0.50

Sift4G

Benign

0.53

Polyphen

0.018

Vest4

0.25

MutPred

0.34

Gain of disorder (P = 0.0485)

MVP

0.52

MPC

0.19

ClinPred

0.082

GERP RS

-0.11

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.032

gMVP

0.34

Mutation Taster

=89/11

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over