Variant 3-186854253-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM1

The NM_004797.4(ADIPOQ):c.284C>T(p.Pro95Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000192 in 1,613,502 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

ADIPOQ
NM_004797.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.29

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 Uncertain_significance. Variant got 2 ACMG points.

PM1

In a modified_residue 4-hydroxyproline; partial (size 0) in uniprot entity ADIPO_HUMAN

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ADIPOQ	NM_004797.4 linkuse as main transcript	c.284C>T	p.Pro95Leu	missense_variant	3/3	ENST00000320741.7
ADIPOQ-AS1	NR_046662.2 linkuse as main transcript	n.2000G>A		non_coding_transcript_exon_variant	2/4
ADIPOQ	NM_001177800.2 linkuse as main transcript	c.284C>T	p.Pro95Leu	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
ADIPOQ	ENST00000320741.7 linkuse as main transcript	c.284C>T	p.Pro95Leu	missense_variant	3/3	1	NM_004797.4	P1
ADIPOQ	ENST00000444204.2 linkuse as main transcript	c.284C>T	p.Pro95Leu	missense_variant	4/4	1		P1
ADIPOQ-AS1	ENST00000422718.1 linkuse as main transcript	n.1871G>A		non_coding_transcript_exon_variant	1/3	5

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251170

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135756

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000205

AC:

AN:

1461336

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

726860

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000453

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000810

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152166

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 28, 2024

The c.284C>T (p.P95L) alteration is located in exon 3 (coding exon 2) of the ADIPOQ gene. This alteration results from a C to T substitution at nucleotide position 284, causing the proline (P) at amino acid position 95 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Uncertain

0.033

BayesDel_noAF

Uncertain

-0.020

Cadd

Pathogenic

Dann

Uncertain

1.0

DEOGEN2

Pathogenic

0.89

D;D

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Uncertain

0.95

M_CAP

Pathogenic

0.45

MetaRNN

Uncertain

0.59

D;D

MetaSVM

Pathogenic

0.95

MutationAssessor

Benign

1.9

L;L

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.60

PROVEAN

Uncertain

-4.2

D;D

REVEL

Pathogenic

0.73

Sift

Uncertain

0.0060

D;D

Sift4G

Uncertain

0.016

D;D

Polyphen

1.0

D;D

Vest4

0.36

MutPred

0.52

Loss of disorder (P = 0.0345);Loss of disorder (P = 0.0345);

MVP

0.98

ClinPred

0.99

GERP RS

4.6

Varity_R

0.38

gMVP

0.46

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