1-202941611-C-G

Variant names:

• chr1-202941611-C-G
• rs139371614
• NM_015999.6:c.1090G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_015999.6(ADIPOR1):​c.1090G>C​(p.Gly364Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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. G364S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ADIPOR1 NM_015999.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.98
• Publications: 1 publications found

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32369113).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADIPOR1	NM_015999.6	MANE Select	c.1090G>C	p.Gly364Arg	missense	Exon 8 of 8	NP_057083.2
	ADIPOR1	NM_001290553.2		c.1090G>C	p.Gly364Arg	missense	Exon 8 of 8	NP_001277482.1	Q96A54
	ADIPOR1	NM_001290557.1		c.1090G>C	p.Gly364Arg	missense	Exon 9 of 9	NP_001277486.1	Q96A54

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADIPOR1	ENST00000340990.10	TSL:1 MANE Select	c.1090G>C	p.Gly364Arg	missense	Exon 8 of 8	ENSP00000341785.5	Q96A54
	ADIPOR1	ENST00000367254.7	TSL:1	c.*305G>C		3_prime_UTR	Exon 7 of 7	ENSP00000356223.3	F8W782
	ADIPOR1	ENST00000855702.1		c.1090G>C	p.Gly364Arg	missense	Exon 8 of 8	ENSP00000525761.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Benign	-0.055	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	24
DANN	Benign	0.38
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.024
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-1.0	T
PhyloP100		5.0
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-0.13	N
REVEL	Benign	0.15
Sift	Benign	0.11	T
Sift4G	Benign	0.51	T
Polyphen		0.10	B
Vest4		0.58
MutPred		0.46		Gain of helix (P = 0.0128)
MVP		0.23
MPC		1.1
ClinPred		0.58	D
GERP RS		5.9
Varity_R		0.22
gMVP		0.92
Mutation Taster		=42/58	disease causing

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

Other links and lift over

dbSNP: rs139371614; hg19: chr1-202910739;