chr1-54009095-G-C

Variant names:

• chr1-54009095-G-C
• NM_001010978.4:c.505C>G

Variant summary

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

The NM_001010978.4(LDLRAD1):​c.505C>G​(p.Arg169Gly) 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. 15/22 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. R169H) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: LDLRAD1 NM_001010978.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.09
• Publications: 0 publications found

Genes affected

LDLRAD1 (HGNC:32069): (low density lipoprotein receptor class A domain containing 1) Predicted to be integral component of 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=0.16160217).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001010978.4. 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
	LDLRAD1	NM_001010978.4	MANE Select	c.505C>G	p.Arg169Gly	missense	Exon 6 of 6	NP_001010978.2	Q5T700-1
	LDLRAD1	NM_001276392.2		c.388C>G	p.Arg130Gly	missense	Exon 4 of 4	NP_001263321.1	Q5T700-2
	LDLRAD1	NM_001276393.2		c.376C>G	p.Arg126Gly	missense	Exon 5 of 5	NP_001263322.1	Q5T700-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LDLRAD1	ENST00000371360.2	TSL:1 MANE Select	c.505C>G	p.Arg169Gly	missense	Exon 6 of 6	ENSP00000360411.1	Q5T700-1
	LDLRAD1	ENST00000420619.5	TSL:1	c.388C>G	p.Arg130Gly	missense	Exon 4 of 4	ENSP00000411017.1	Q5T700-2
	LDLRAD1	ENST00000545928.5	TSL:1	c.376C>G	p.Arg126Gly	missense	Exon 5 of 5	ENSP00000445871.1	Q5T700-4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

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	0.11
BayesDel_addAF	Benign	-0.018	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.025	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.58	T
MutationAssessor	Benign	1.9	L
PhyloP100		2.1
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.19
Sift	Benign	0.18	T
Sift4G	Benign	0.46	T
Polyphen		0.0010	B
Vest4		0.10
MutPred		0.47		Gain of glycosylation at S172 (P = 0.0433)
MVP		0.74
MPC		0.051
ClinPred		0.51	D
GERP RS		1.4
Varity_R		0.12
gMVP		0.53
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr1-54474768;