dbSNP rs2102480253: ADIPOR1:p.Tyr310Cys (chr1-202942095-T-C) – ACMG Classification: Likely_pathogenic (8 pts)

Variant summary

Our verdict is Likely pathogenic. The variant received 8 ACMG points: 8P and 0B. PM2PP3_StrongPP5_Moderate

The NM_015999.6(ADIPOR1):c.929A>G(p.Tyr310Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y310N) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

ADIPOR1
NM_015999.6 missense

Scores

Clinical Significance

Pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 7.93

Publications

1 publications found

Variant links:

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]

ADIPOR1 Gene-Disease associations (from GenCC):

retinitis pigmentosa
Inheritance: AD Classification: LIMITED Submitted by: Franklin by Genoox

ADIPOR1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 8 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.974

PP5

Variant 1-202942095-T-C is Pathogenic according to our data. Variant chr1-202942095-T-C is described in ClinVar as Pathogenic. ClinVar VariationId is 1403201.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015999.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ADIPOR1	NM_015999.6	MANE Select	c.929A>G	p.Tyr310Cys	missense	Exon 7 of 8	NP_057083.2
ADIPOR1	NM_001290553.2		c.929A>G	p.Tyr310Cys	missense	Exon 7 of 8	NP_001277482.1	Q96A54
ADIPOR1	NM_001290557.1		c.929A>G	p.Tyr310Cys	missense	Exon 8 of 9	NP_001277486.1	Q96A54

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ADIPOR1	ENST00000340990.10	TSL:1 MANE Select	c.929A>G	p.Tyr310Cys	missense	Exon 7 of 8	ENSP00000341785.5	Q96A54
ADIPOR1	ENST00000367254.7	TSL:1	c.*144A>G		3_prime_UTR	Exon 6 of 7	ENSP00000356223.3	F8W782
ADIPOR1	ENST00000855702.1		c.929A>G	p.Tyr310Cys	missense	Exon 7 of 8	ENSP00000525761.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Pathogenic

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.99

BayesDel_addAF

Pathogenic

0.33

BayesDel_noAF

Pathogenic

0.23

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.49

Eigen

Pathogenic

1.0

Eigen_PC

Pathogenic

0.98

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

1.0

M_CAP

Benign

0.015

MetaRNN

Pathogenic

0.97

MetaSVM

Uncertain

0.19

PhyloP100

7.9

PrimateAI

Pathogenic

0.93

PROVEAN

Pathogenic

-7.9

REVEL

Uncertain

0.58

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0020

Polyphen

1.0

Vest4

0.97

MutPred

0.89

Loss of catalytic residue at L305 (P = 0.1094)

MVP

0.71

MPC

2.3

ClinPred

1.0

GERP RS

6.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.94

gMVP

0.99

Mutation Taster

=4/96

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over