3-186854237-G-A

Position:

chr3-186854237-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PP3BP4_StrongBP6_Very_StrongBS2

The NM_004797.4(ADIPOQ):c.268G>A(p.Gly90Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00317 in 1,613,664 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0028 ( 2 hom., cov: 31)

Exomes 𝑓: 0.0032 ( 15 hom. )

Consequence

ADIPOQ
NM_004797.4 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 9.94

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

PP3

Multiple lines of computational evidence support a deleterious effect 10: AlphaMissense, BayesDel_addAF, BayesDel_noAF, Cadd, Eigen, M_CAP, MutationAssessor, phyloP100way_vertebrate, PROVEAN, REVEL [when max_spliceai, FATHMM_MKL, MetaRNN, MutationTaster was below the threshold]

BP4

Computational evidence support a benign effect (MetaRNN=0.025646985).

BP6

Variant 3-186854237-G-A is Benign according to our data. Variant chr3-186854237-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 789279.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 431 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ADIPOQ	NM_004797.4 linkuse as main transcript	c.268G>A	p.Gly90Ser	missense_variant	3/3	ENST00000320741.7
ADIPOQ-AS1	NR_046662.2 linkuse as main transcript	n.2016C>T		non_coding_transcript_exon_variant	2/4
ADIPOQ	NM_001177800.2 linkuse as main transcript	c.268G>A	p.Gly90Ser	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
ADIPOQ	ENST00000320741.7 linkuse as main transcript	c.268G>A	p.Gly90Ser	missense_variant	3/3	1	NM_004797.4	P1
ADIPOQ	ENST00000444204.2 linkuse as main transcript	c.268G>A	p.Gly90Ser	missense_variant	4/4	1		P1
ADIPOQ-AS1	ENST00000422718.1 linkuse as main transcript	n.1887C>T		non_coding_transcript_exon_variant	1/3	5

Frequencies

GnomAD3 genomes

AF:

0.00283

AC:

431

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000748

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00190

Gnomad ASJ

AF:

0.00605

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.00104

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00478

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00299

AC:

752

AN:

251152

Hom.:

AF XY:

0.00309

AC XY:

420

AN XY:

135730

show subpopulations

Gnomad AFR exome

AF:

0.000431

Gnomad AMR exome

AF:

0.00223

Gnomad ASJ exome

AF:

0.00609

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000654

Gnomad FIN exome

AF:

0.000694

Gnomad NFE exome

AF:

0.00482

Gnomad OTH exome

AF:

0.00392

GnomAD4 exome

AF:

0.00320

AC:

4679

AN:

1461326

Hom.:

Cov.:

AF XY:

0.00322

AC XY:

2338

AN XY:

726886

show subpopulations

Gnomad4 AFR exome

AF:

0.00123

Gnomad4 AMR exome

AF:

0.00224

Gnomad4 ASJ exome

AF:

0.00567

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000835

Gnomad4 FIN exome

AF:

0.000674

Gnomad4 NFE exome

AF:

0.00358

Gnomad4 OTH exome

AF:

0.00394

GnomAD4 genome

AF:

0.00283

AC:

431

AN:

152338

Hom.:

Cov.:

AF XY:

0.00278

AC XY:

207

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.000746

Gnomad4 AMR

AF:

0.00189

Gnomad4 ASJ

AF:

0.00605

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.00104

Gnomad4 NFE

AF:

0.00478

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00431

Hom.:

Bravo

AF:

0.00301

TwinsUK

AF:

0.00485

AC:

ALSPAC

AF:

0.00571

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00581

AC:

ExAC

AF:

0.00302

AC:

367

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00589

EpiControl

AF:

0.00616

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

ADIPOQ-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 21, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.74

BayesDel_addAF

Pathogenic

0.26

BayesDel_noAF

Pathogenic

0.60

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.97

D;D

Eigen

Pathogenic

1.0

Eigen_PC

Pathogenic

0.92

FATHMM_MKL

Pathogenic

1.0

M_CAP

Pathogenic

0.43

MetaRNN

Benign

0.026

T;T

MetaSVM

Pathogenic

0.82

MutationAssessor

Pathogenic

3.4

M;M

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.75

PROVEAN

Pathogenic

-5.7

D;D

REVEL

Pathogenic

0.97

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;D

Vest4

0.72

MVP

0.94

ClinPred

0.067

GERP RS

5.5

Varity_R

0.97

gMVP

0.85

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over