Variant 11-36081659-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_174902.4(LDLRAD3):c.200C>G(p.Ala67Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,888 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

LDLRAD3
NM_174902.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.52

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=0.1820989).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
LDLRAD3	NM_174902.4 linkuse as main transcript	c.200C>G	p.Ala67Gly	missense_variant	3/6	ENST00000315571.6	NP_777562.1
LDLRAD3	NM_001304263.2 linkuse as main transcript	c.53C>G	p.Ala18Gly	missense_variant	2/5		NP_001291192.1
LDLRAD3	NM_001304264.2 linkuse as main transcript	c.-280C>G		5_prime_UTR_variant	2/6		NP_001291193.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LDLRAD3	ENST00000315571.6 linkuse as main transcript	c.200C>G	p.Ala67Gly	missense_variant	3/6	1	NM_174902.4	ENSP00000318607	P1	Q86YD5-1
LDLRAD3	ENST00000528989.5 linkuse as main transcript	c.53C>G	p.Ala18Gly	missense_variant	2/5	1		ENSP00000433954		Q86YD5-2
LDLRAD3	ENST00000524419.5 linkuse as main transcript	c.53C>G	p.Ala18Gly	missense_variant	2/6	5		ENSP00000434313
LDLRAD3	ENST00000532490.1 linkuse as main transcript	n.154C>G		non_coding_transcript_exon_variant	3/5	4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461888

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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:

0.00

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

May 24, 2024

The c.200C>G (p.A67G) alteration is located in exon 3 (coding exon 3) of the LDLRAD3 gene. This alteration results from a C to G substitution at nucleotide position 200, causing the alanine (A) at amino acid position 67 to be replaced by a glycine (G). 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

0.11

BayesDel_addAF

Uncertain

0.063

BayesDel_noAF

Benign

-0.15

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.015

.;.;T

Eigen

Benign

-0.50

Eigen_PC

Benign

-0.34

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.76

T;T;T

M_CAP

Benign

0.081

MetaRNN

Benign

0.18

T;T;T

MetaSVM

Benign

-0.37

MutationAssessor

Benign

1.1

.;.;L

MutationTaster

Benign

0.97

N;N;N

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-1.5

N;N;N

REVEL

Benign

0.22

Sift

Benign

0.041

D;D;T

Sift4G

Benign

0.23

T;D;T

Polyphen

0.0010

.;.;B

Vest4

0.27

MutPred

0.26

.;.;Gain of ubiquitination at K62 (P = 0.0817);

MVP

0.73

MPC

0.19

ClinPred

0.35

GERP RS

3.8

Varity_R

0.063

gMVP

0.41

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

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