dbSNP rs121917815: ADIPOQ:p.Arg112Gly (chr3-186854303-C-G) – ACMG Classification: Uncertain_significance (5 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PM2PM5PP3

The NM_004797.4(ADIPOQ):c.334C>G(p.Arg112Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. R112C) has been classified as Pathogenic.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ADIPOQ
NM_004797.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.62

Publications

30 publications found

Variant links:

Genes affected

ADIPOQ (HGNC:13633): (adiponectin, C1Q and collagen domain containing) This gene is expressed in adipose tissue exclusively. It encodes a protein with similarity to collagens X and VIII and complement factor C1q. The encoded protein circulates in the plasma and is involved with metabolic and hormonal processes. Mutations in this gene are associated with adiponectin deficiency. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Apr 2010]

ADIPOQ links:

ADIPOQ-AS1 (HGNC:40648): (ADIPOQ antisense RNA 1)

ADIPOQ-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PM5

Other missense variant is known to change same aminoacid residue: Variant chr3-186854303-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 4990.Status of the report is no_assertion_criteria_provided, 0 stars.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.785

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADIPOQ	NM_004797.4 link	c.334C>G	p.Arg112Gly	missense_variant	Exon 3 of 3	ENST00000320741.7	NP_004788.1	Q15848A8K660
ADIPOQ	NM_001177800.2 link	c.334C>G	p.Arg112Gly	missense_variant	Exon 4 of 4		NP_001171271.1	Q15848A8K660B2R773
ADIPOQ-AS1	NR_046662.2 link	n.1950G>C		non_coding_transcript_exon_variant	Exon 2 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ADIPOQ	ENST00000320741.7 link	c.334C>G	p.Arg112Gly	missense_variant	Exon 3 of 3	1	NM_004797.4	ENSP00000320709.2	Q15848
ADIPOQ	ENST00000444204.2 link	c.334C>G	p.Arg112Gly	missense_variant	Exon 4 of 4	1		ENSP00000389814.2	Q15848
ADIPOQ-AS1	ENST00000422718.1 link	n.1821G>C		non_coding_transcript_exon_variant	Exon 1 of 3	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461890

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727246

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.0000224

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1112012

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.43

BayesDel_addAF

Pathogenic

0.26

BayesDel_noAF

Uncertain

0.13

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.74

D;D

Eigen

Pathogenic

0.76

Eigen_PC

Pathogenic

0.74

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.94

.;D

M_CAP

Uncertain

0.086

MetaRNN

Pathogenic

0.79

D;D

MetaSVM

Uncertain

0.49

MutationAssessor

Pathogenic

3.4

M;M

PhyloP100

4.6

PrimateAI

Benign

0.44

PROVEAN

Pathogenic

-5.3

D;D

REVEL

Uncertain

0.64

Sift

Uncertain

0.0020

D;D

Sift4G

Benign

0.079

T;T

Polyphen

0.99

D;D

Vest4

0.62

MutPred

0.54

Gain of glycosylation at Y111 (P = 0.0173);Gain of glycosylation at Y111 (P = 0.0173);

MVP

0.98

ClinPred

1.0

GERP RS

5.5

Varity_R

0.92

gMVP

0.67

Mutation Taster

=38/62

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

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rs121917815

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over