1-202941699-G-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_015999.6(ADIPOR1):​c.1002C>A​(p.Phe334Leu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: ADIPOR1 NM_015999.6 missense, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.02

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 4 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADIPOR1	NM_015999.6	c.1002C>A	p.Phe334Leu	missense_variant, splice_region_variant	Exon 8 of 8	ENST00000340990.10	NP_057083.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADIPOR1	ENST00000340990.10	c.1002C>A	p.Phe334Leu	missense_variant, splice_region_variant	Exon 8 of 8	1	NM_015999.6	ENSP00000341785.5
ADIPOR1	ENST00000367254.7	c.*217C>A		splice_region_variant	Exon 7 of 7	1		ENSP00000356223.3
ADIPOR1	ENST00000367254	c.*217C>A		3_prime_UTR_variant	Exon 7 of 7	1		ENSP00000356223.3
ADIPOR1	ENST00000495562.5	n.1236C>A		splice_region_variant, non_coding_transcript_exon_variant	Exon 3 of 3	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.88
BayesDel_addAF	Uncertain	0.035	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.37	T
Eigen	Benign	0.056
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.0088	T
MetaRNN	Pathogenic	0.89	D
MetaSVM	Benign	-1.1	T
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		0.51
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

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr1-202910827;