NM_174902.4:c.200C>T

Variant names:

• chr11-36081659-C-T
• NM_174902.4:c.200C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_174902.4(LDLRAD3):​c.200C>T​(p.Ala67Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A67G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: LDLRAD3 NM_174902.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.52
• Publications: 0 publications found

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]

ACMG classification

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=0.1504561).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LDLRAD3	NM_174902.4	MANE Select	c.200C>T	p.Ala67Val	missense	Exon 3 of 6	NP_777562.1	Q86YD5-1
	LDLRAD3	NM_001304263.2		c.53C>T	p.Ala18Val	missense	Exon 2 of 5	NP_001291192.1	Q86YD5-2
	LDLRAD3	NM_001304264.2		c.-280C>T		5_prime_UTR	Exon 2 of 6	NP_001291193.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LDLRAD3	ENST00000315571.6	TSL:1 MANE Select	c.200C>T	p.Ala67Val	missense	Exon 3 of 6	ENSP00000318607.5	Q86YD5-1
	LDLRAD3	ENST00000528989.5	TSL:1	c.53C>T	p.Ala18Val	missense	Exon 2 of 5	ENSP00000433954.1	Q86YD5-2
	LDLRAD3	ENST00000872891.1		c.200C>T	p.Ala67Val	missense	Exon 3 of 6	ENSP00000542950.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Uncertain	0.042	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	18
DANN	Uncertain	0.97
DEOGEN2	Benign	0.013	T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.39
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.083	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.53	T
MutationAssessor	Benign	0.87	L
PhyloP100		2.5
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.22
Sift	Benign	0.13	T
Sift4G	Benign	0.32	T
Polyphen		0.0	B
Vest4		0.16
MutPred		0.27		Gain of methylation at K66 (P = 0.0351)
MVP		0.71
MPC		0.19
ClinPred		0.25	T
GERP RS		3.8
Varity_R		0.037
gMVP		0.38
Mutation Taster		=87/13	polymorphism

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

Other links and lift over

hg19: chr11-36103209;