1-202941699-G-C

Variant names:

• chr1-202941699-G-C
• rs144099149
• NM_015999.6:c.1002C>G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_015999.6(ADIPOR1):​c.1002C>G​(p.Phe334Leu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,296 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. F334F) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ADIPOR1 NM_015999.6 missense, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.02
• Publications: 0 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.89

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.1002C>G	p.Phe334Leu	missense splice_region	Exon 8 of 8	NP_057083.2
	ADIPOR1	NM_001290553.2		c.1002C>G	p.Phe334Leu	missense splice_region	Exon 8 of 8	NP_001277482.1	Q96A54
	ADIPOR1	NM_001290557.1		c.1002C>G	p.Phe334Leu	missense splice_region	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.1002C>G	p.Phe334Leu	missense splice_region	Exon 8 of 8	ENSP00000341785.5	Q96A54
	ADIPOR1	ENST00000367254.7	TSL:1	c.*217C>G		splice_region	Exon 7 of 7	ENSP00000356223.3	F8W782
	ADIPOR1	ENST00000367254.7	TSL:1	c.*217C>G		3_prime_UTR	Exon 7 of 7	ENSP00000356223.3	F8W782

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457296 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 724944

African (AFR) AF: 0.0000304 AC: 1 AN: 32928

American (AMR) AF: 0.00 AC: 0 AN: 43268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25910

East Asian (EAS) AF: 0.00 AC: 0 AN: 39682

South Asian (SAS) AF: 0.00 AC: 0 AN: 85284

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53368

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5742

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110954

Other (OTH) AF: 0.00 AC: 0 AN: 60160

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.88
BayesDel_addAF	Uncertain	0.035	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.37	T
Eigen	Benign	0.056
Eigen_PC	Benign	0.16
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.0086	T
MetaRNN	Pathogenic	0.89	D
MetaSVM	Benign	-1.1	T
PhyloP100		2.0
PrimateAI	Pathogenic	0.85	D
PROVEAN	Pathogenic	-4.4	D
REVEL	Benign	0.29
Sift	Benign	0.10	T
Sift4G	Benign	0.22	T
Polyphen		0.66	P
Vest4		0.79
MutPred		0.78		Loss of methylation at K329 (P = 0.0793)
MVP		0.50
MPC		1.7
ClinPred		0.98	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.60
gMVP		0.94
Mutation Taster		=32/68	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs144099149; hg19: chr1-202910827;