rs886039240

chr1-202951039-TG-T

Variant summary

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

The NM_015999.6(ADIPOR1):c.31del(p.Gln11ArgfsTer24) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ADIPOR1 NM_015999.6 frameshift
• Clinical Significance: Uncertain significance criteria provided, single submitter U:2
• Conservation: PhyloP100: 4.21

Genes affected

ADIPOR1 (HGNC:24040): (adiponectin receptor 1) This gene encodes a protein which acts as a receptor for adiponectin, a hormone secreted by adipocytes which regulates fatty acid catabolism and glucose levels. Binding of adiponectin to the encoded protein results in activation of an AMP-activated kinase signaling pathway which affects levels of fatty acid oxidation and insulin sensitivity. A pseudogene of this gene is located on chromosome 14. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Mar 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/exons	MANE	UniProt
ADIPOR1	NM_015999.6	c.31del	p.Gln11ArgfsTer24	frameshift_variant	2/8	ENST00000340990.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADIPOR1	ENST00000340990.10	c.31del	p.Gln11ArgfsTer24	frameshift_variant	2/8	1	NM_015999.6	P1
ADIPOR1	ENST00000367254.7	c.31del	p.Gln11ArgfsTer24	frameshift_variant	2/7	1
ADIPOR1	ENST00000417068.5	c.31del	p.Gln11ArgfsTer24	frameshift_variant	3/7	3
ADIPOR1	ENST00000426229.1	c.31del	p.Gln11ArgfsTer24	frameshift_variant	3/6	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:2

Uncertain significance, no assertion criteria provided	literature only	OMIM	Oct 03, 2016	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Invitae	Jan 06, 2022	In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. ClinVar contains an entry for this variant (Variation ID: 264709). This premature translational stop signal has been observed in individual(s) with autosomal recessive syndromic retinitis pigmentosa (PMID: 26662040). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln11Argfs*24) in the ADIPOR1 gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in ADIPOR1 cause disease. -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs886039240; hg19: chr1-202920167;