rs1320478096

Variant names:

• chr2-74528757-C-A
• NM_181575.5:c.518G>T

Your query was ambiguous. Multiple possible variants found:

• chr2-74528757-C-A
• chr2-74528757-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_181575.5(AUP1):​c.518G>T​(p.Arg173Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,444,572 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R173H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: AUP1 NM_181575.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.758

Genes affected

AUP1 (HGNC:891): (AUP1 lipid droplet regulating VLDL assembly factor) The protein encoded this gene is involved in several pathways including quality control of misfolded proteins in the endoplasmic reticulum and lipid droplet accumulation. Lipid droplets are organelles in the cytoplasm that store neutral lipids such as cholesterol esters and trigylycerides to prevent the overabundance of free cholesterol and fatty acids in cells, but also to act as storage for other metabolic processes, such as membrane biogenesis. Reduced expression of this gene results in reduced lipid droplet clustering, a function that is dependent on ubiquitination of the protein. This protein contains multiple domains including a hydrophobic N-terminal domain, an acetyltranferase domain, a ubiquitin-binding CUE domain, and a UBE2B2-binding domain (G2BR). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2014]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AUP1	NM_181575.5	c.518G>T	p.Arg173Leu	missense_variant	Exon 4 of 12	ENST00000377526.4	NP_853553.1
AUP1	NR_126510.2	n.595G>T		non_coding_transcript_exon_variant	Exon 4 of 12
AUP1	NR_126511.2	n.791G>T		non_coding_transcript_exon_variant	Exon 3 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AUP1	ENST00000377526.4	c.518G>T	p.Arg173Leu	missense_variant	Exon 4 of 12	1	NM_181575.5	ENSP00000366748.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1444572 Hom.: 0 Cov.: 33 AF XY: 0.00000279 AC XY: 2 AN XY: 717970

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000506

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.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Benign	19
DANN	Uncertain	0.99
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.61	D
LIST_S2	Uncertain	0.95	D
M_CAP	Uncertain	0.15	D
MetaRNN	Uncertain	0.56	D
MetaSVM	Uncertain	-0.19	T
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-4.3	D
REVEL	Uncertain	0.53
Sift	Uncertain	0.018	D
Sift4G	Uncertain	0.036	D
Vest4		0.58
MVP		0.68
MPC		0.52
ClinPred		0.99	D
GERP RS		0.40
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.15
gMVP		0.63

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-74755884;