1-54009095-G-C

Position:

• chr1-54009095-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 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. 14/21 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. 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

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

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=0.16160217).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LDLRAD1	NM_001010978.4	c.505C>G	p.Arg169Gly	missense_variant	6/6	ENST00000371360.2	NP_001010978.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LDLRAD1	ENST00000371360.2	c.505C>G	p.Arg169Gly	missense_variant	6/6	1	NM_001010978.4	ENSP00000360411.1
LDLRAD1	ENST00000420619.5	c.388C>G	p.Arg130Gly	missense_variant	4/4	1		ENSP00000411017.1
LDLRAD1	ENST00000545928.5	c.376C>G	p.Arg126Gly	missense_variant	5/5	1		ENSP00000445871.1
LDLRAD1	ENST00000371362.7	c.238C>G	p.Arg80Gly	missense_variant	4/4	1		ENSP00000360413.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 10, 2024

The c.505C>G (p.R169G) alteration is located in exon 6 (coding exon 6) of the LDLRAD1 gene. This alteration results from a C to G substitution at nucleotide position 505, causing the arginine (R) at amino acid position 169 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	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;T;T;T
M_CAP	Benign	0.025	D
MetaRNN	Benign	0.16	T;T;T;T
MetaSVM	Benign	-0.58	T
MutationAssessor	Benign	1.9	.;.;.;L
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-2.2	N;N;D;N
REVEL	Benign	0.19
Sift	Benign	0.18	T;T;T;T
Sift4G	Benign	0.46	T;T;T;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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-54474768;