3-186854300-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

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 š‘“: 6.8e-7 ( 0 hom. )

Consequence

ADIPOQ
NM_004797.4 missense

Scores

7
12

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.271
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-AS1 (HGNC:40648): (ADIPOQ antisense RNA 1)

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ACMG classification

Classification made for transcript

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
ADIPOQNM_004797.4 linkc.331T>G p.Tyr111Asp missense_variant Exon 3 of 3 ENST00000320741.7 NP_004788.1 Q15848A8K660
ADIPOQNM_001177800.2 linkc.331T>G p.Tyr111Asp missense_variant Exon 4 of 4 NP_001171271.1 Q15848A8K660B2R773
ADIPOQ-AS1NR_046662.2 linkn.1953A>C non_coding_transcript_exon_variant Exon 2 of 4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ADIPOQENST00000320741.7 linkc.331T>G p.Tyr111Asp missense_variant Exon 3 of 3 1 NM_004797.4 ENSP00000320709.2 Q15848
ADIPOQENST00000444204.2 linkc.331T>G p.Tyr111Asp missense_variant Exon 4 of 4 1 ENSP00000389814.2 Q15848
ADIPOQ-AS1ENST00000422718.1 linkn.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
show subpopulations
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; API