3-186854656-C-A

Position:

• chr3-186854656-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004797.4(ADIPOQ):​c.687C>A​(p.Asp229Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: ADIPOQ NM_004797.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.147

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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08417541).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADIPOQ	NM_004797.4	c.687C>A	p.Asp229Glu	missense_variant	3/3	ENST00000320741.7
ADIPOQ-AS1	NR_046662.2	n.1597G>T		non_coding_transcript_exon_variant	2/4
ADIPOQ	NM_001177800.2	c.687C>A	p.Asp229Glu	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADIPOQ	ENST00000320741.7	c.687C>A	p.Asp229Glu	missense_variant	3/3	1	NM_004797.4	P1
ADIPOQ	ENST00000444204.2	c.687C>A	p.Asp229Glu	missense_variant	4/4	1		P1
ADIPOQ-AS1	ENST00000422718.1	n.1468G>T		non_coding_transcript_exon_variant	1/3	5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 19, 2024

The c.687C>A (p.D229E) alteration is located in exon 3 (coding exon 2) of the ADIPOQ gene. This alteration results from a C to A substitution at nucleotide position 687, causing the aspartic acid (D) at amino acid position 229 to be replaced by a glutamic acid (E). 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	0.12
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	21
DANN	Benign	0.76
DEOGEN2	Benign	0.28	T;T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.81	.;T
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.084	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.015	N;N
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.13	N;N
REVEL	Benign	0.076
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.24	B;B
Vest4		0.019
MutPred		0.46		Gain of glycosylation at Y225 (P = 0.0205);Gain of glycosylation at Y225 (P = 0.0205);
MVP		0.59
ClinPred		0.22	T
GERP RS		3.9
Varity_R		0.12
gMVP		0.20

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: rs1711927755; hg19: chr3-186572445;