3-186854303-C-G

Position:

• chr3-186854303-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

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.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ADIPOQ NM_004797.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.62

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:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.785

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADIPOQ	NM_004797.4	c.334C>G	p.Arg112Gly	missense_variant	3/3	ENST00000320741.7	NP_004788.1
ADIPOQ	NM_001177800.2	c.334C>G	p.Arg112Gly	missense_variant	4/4		NP_001171271.1
ADIPOQ-AS1	NR_046662.2	n.1950G>C		non_coding_transcript_exon_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADIPOQ	ENST00000320741.7	c.334C>G	p.Arg112Gly	missense_variant	3/3	1	NM_004797.4	ENSP00000320709.2
ADIPOQ	ENST00000444204.2	c.334C>G	p.Arg112Gly	missense_variant	4/4	1		ENSP00000389814.2
ADIPOQ-AS1	ENST00000422718.1	n.1821G>C		non_coding_transcript_exon_variant	1/3	5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461890 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727246

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

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: 0.00000180

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	Uncertain	0.43
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Uncertain	0.13
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.74	D;D
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	.;D
M_CAP	Uncertain	0.086	D
MetaRNN	Pathogenic	0.79	D;D
MetaSVM	Uncertain	0.49	D
MutationAssessor	Pathogenic	3.4	M;M
PrimateAI	Benign	0.44	T
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	D
GERP RS		5.5
Varity_R		0.92
gMVP		0.67

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

Other links and lift over

dbSNP: rs121917815; hg19: chr3-186572092;