12-1772941-A-T

Variant names:

• chr12-1772941-A-T
• rs1159479226
• NM_024551.3:c.271A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024551.3(ADIPOR2):​c.271A>T​(p.Met91Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,220 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M91V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ADIPOR2 NM_024551.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.72
• Publications: 0 publications found

Genes affected

ADIPOR2 (HGNC:24041): (adiponectin receptor 2) The adiponectin receptors, ADIPOR1 (MIM 607945) and ADIPOR2, serve as receptors for globular and full-length adiponectin (MIM 605441) and mediate increased AMPK (see MIM 602739) and PPAR-alpha (PPARA; MIM 170998) ligand activities, as well as fatty acid oxidation and glucose uptake by adiponectin (Yamauchi et al., 2003 [PubMed 12802337]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24643573).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024551.3. 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
	ADIPOR2	NM_024551.3	MANE Select	c.271A>T	p.Met91Leu	missense	Exon 3 of 8	NP_078827.2
	ADIPOR2	NM_001375363.1		c.271A>T	p.Met91Leu	missense	Exon 3 of 9	NP_001362292.1
	ADIPOR2	NM_001375364.1		c.271A>T	p.Met91Leu	missense	Exon 4 of 9	NP_001362293.1	Q86V24

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADIPOR2	ENST00000357103.5	TSL:1 MANE Select	c.271A>T	p.Met91Leu	missense	Exon 3 of 8	ENSP00000349616.4	Q86V24
	ADIPOR2	ENST00000878990.1		c.349A>T	p.Met117Leu	missense	Exon 4 of 10	ENSP00000549049.1
	ADIPOR2	ENST00000878964.1		c.271A>T	p.Met91Leu	missense	Exon 3 of 9	ENSP00000549023.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461220 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726886

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33466

American (AMR) AF: 0.00 AC: 0 AN: 44664

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.00 AC: 0 AN: 86056

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111682

Other (OTH) AF: 0.00 AC: 0 AN: 60366

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.49
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.18
CADD	Benign	23
DANN	Benign	0.96
DEOGEN2	Benign	0.13	T
Eigen	Benign	0.0046
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Pathogenic	0.99	D
M_CAP	Benign	0.052	D
MetaRNN	Benign	0.25	T
MetaSVM	Uncertain	0.19	D
PhyloP100		8.7
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-0.66	N
REVEL	Uncertain	0.41
Sift	Benign	0.10	T
Sift4G	Benign	0.41	T
Polyphen		0.061	B
Vest4		0.49
MutPred		0.45		Gain of catalytic residue at M88 (P = 0)
MVP		0.90
MPC		0.83
ClinPred		0.69	D
GERP RS		5.8
Varity_R		0.15
gMVP		0.89
Mutation Taster		=69/31	polymorphism

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: rs1159479226; hg19: chr12-1882107;