3-186854237-G-T

Variant names:

• chr3-186854237-G-T
• NM_004797.4:c.268G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PP3_Strong BS2

The NM_004797.4(ADIPOQ):​c.268G>T​(p.Gly90Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000753 in 1,461,326 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. G90S) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000075 (0 hom.)
• Consequence: ADIPOQ NM_004797.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.94

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

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.989
• BS2: High AC in GnomAdExome4 at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADIPOQ	NM_004797.4	c.268G>T	p.Gly90Cys	missense_variant	Exon 3 of 3	ENST00000320741.7	NP_004788.1
ADIPOQ	NM_001177800.2	c.268G>T	p.Gly90Cys	missense_variant	Exon 4 of 4		NP_001171271.1
ADIPOQ-AS1	NR_046662.2	n.2016C>A		non_coding_transcript_exon_variant	Exon 2 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADIPOQ	ENST00000320741.7	c.268G>T	p.Gly90Cys	missense_variant	Exon 3 of 3	1	NM_004797.4	ENSP00000320709.2
ADIPOQ	ENST00000444204.2	c.268G>T	p.Gly90Cys	missense_variant	Exon 4 of 4	1		ENSP00000389814.2
ADIPOQ-AS1	ENST00000422718.1	n.1887C>A		non_coding_transcript_exon_variant	Exon 1 of 3	5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000753 AC: 11 AN: 1461326 Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9 AN XY: 726886

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000990

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.93
BayesDel_addAF	Pathogenic	0.59	D
BayesDel_noAF	Pathogenic	0.61
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.97	D;D
Eigen	Pathogenic	1.1
Eigen_PC	Pathogenic	0.97
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.96	.;D
M_CAP	Pathogenic	0.50	D
MetaRNN	Pathogenic	0.99	D;D
MetaSVM	Pathogenic	0.96	D
MutationAssessor	Pathogenic	4.3	H;H
PrimateAI	Uncertain	0.77	T
PROVEAN	Pathogenic	-8.6	D;D
REVEL	Pathogenic	0.96
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;D
Vest4		0.82
MutPred		0.93		Loss of catalytic residue at P86 (P = 0.0814);Loss of catalytic residue at P86 (P = 0.0814);
MVP		0.98
ClinPred		1.0	D
GERP RS		5.5
Varity_R		0.97
gMVP		0.90

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-186572026;