3-186854300-T-G

Variant names:

• chr3-186854300-T-G
• NM_004797.4:c.331T>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_004797.4(ADIPOQ):​c.331T>G​(p.Tyr111Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign 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. Y111H) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ADIPOQ NM_004797.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.271

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37384266).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADIPOQ	NM_004797.4	c.331T>G	p.Tyr111Asp	missense_variant	Exon 3 of 3	ENST00000320741.7	NP_004788.1
ADIPOQ	NM_001177800.2	c.331T>G	p.Tyr111Asp	missense_variant	Exon 4 of 4		NP_001171271.1
ADIPOQ-AS1	NR_046662.2	n.1953A>C		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.331T>G	p.Tyr111Asp	missense_variant	Exon 3 of 3	1	NM_004797.4	ENSP00000320709.2
ADIPOQ	ENST00000444204.2	c.331T>G	p.Tyr111Asp	missense_variant	Exon 4 of 4	1		ENSP00000389814.2
ADIPOQ-AS1	ENST00000422718.1	n.1824A>C		non_coding_transcript_exon_variant	Exon 1 of 3	5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461892 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727248

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

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	Benign	0.32
BayesDel_addAF	Uncertain	0.071	D
BayesDel_noAF	Benign	-0.14
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.42	T;T
Eigen	Benign	0.065
Eigen_PC	Benign	0.042
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Uncertain	0.87	.;D
M_CAP	Benign	0.066	D
MetaRNN	Benign	0.37	T;T
MetaSVM	Benign	-0.53	T
MutationAssessor	Uncertain	2.4	M;M
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-2.8	D;D
REVEL	Uncertain	0.47
Sift	Benign	0.19	T;T
Sift4G	Benign	0.20	T;T
Polyphen		0.96	D;D
Vest4		0.38
MutPred		0.45		Gain of relative solvent accessibility (P = 0.005);Gain of relative solvent accessibility (P = 0.005);
MVP		0.92
ClinPred		0.86	D
GERP RS		3.1
Varity_R		0.38
gMVP		0.68

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: chr3-186572089;