NM_004797.4:c.331T>C

Variant names:

• chr3-186854300-T-C
• rs17366743
• NM_004797.4:c.331T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BS1 BS2

The NM_004797.4(ADIPOQ):​c.331T>C​(p.Tyr111His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0277 in 1,614,206 control chromosomes in the GnomAD database, including 727 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.020 (50 hom., cov: 31)
  • Exomes 𝑓: 0.028 (677 hom.)
• Consequence: ADIPOQ NM_004797.4 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.271
• Publications: 91 publications found

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

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0059143007).
• BP6: Variant 3-186854300-T-C is Benign according to our data. Variant chr3-186854300-T-C is described in ClinVar as Benign. ClinVar VariationId is 3042029.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0205 (3118/152328) while in subpopulation NFE AF = 0.0297 (2019/68024). AF 95% confidence interval is 0.0286. There are 50 homozygotes in GnomAd4. There are 1518 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 50 Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004797.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADIPOQ	NM_004797.4	MANE Select	c.331T>C	p.Tyr111His	missense	Exon 3 of 3	NP_004788.1	Q15848
	ADIPOQ	NM_001177800.2		c.331T>C	p.Tyr111His	missense	Exon 4 of 4	NP_001171271.1	A8K660
	ADIPOQ-AS1	NR_046662.2		n.1953A>G		non_coding_transcript_exon	Exon 2 of 4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADIPOQ	ENST00000320741.7	TSL:1 MANE Select	c.331T>C	p.Tyr111His	missense	Exon 3 of 3	ENSP00000320709.2	Q15848
	ADIPOQ	ENST00000444204.2	TSL:1	c.331T>C	p.Tyr111His	missense	Exon 4 of 4	ENSP00000389814.2	Q15848
	ADIPOQ	ENST00000881747.1		c.331T>C	p.Tyr111His	missense	Exon 3 of 3	ENSP00000551806.1

Frequencies

GnomAD3 genomes AF: 0.0205 AC: 3118 AN: 152210 Hom.: 49 Cov.: 31

Gnomad AFR AF: 0.00605

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0125

Gnomad ASJ AF: 0.0372

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.00932

Gnomad FIN AF: 0.0387

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0297

Gnomad OTH AF: 0.0153

GnomAD2 exomes AF: 0.0219 AC: 5516 AN: 251458 AF XY: 0.0227

Gnomad AFR exome AF: 0.00714

Gnomad AMR exome AF: 0.0104

Gnomad ASJ exome AF: 0.0339

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0387

Gnomad NFE exome AF: 0.0291

Gnomad OTH exome AF: 0.0274

GnomAD4 exome AF: 0.0285 AC: 41648 AN: 1461878 Hom.: 677 Cov.: 31 AF XY: 0.0280 AC XY: 20361 AN XY: 727236

African (AFR) AF: 0.00430 AC: 144 AN: 33480

American (AMR) AF: 0.0107 AC: 478 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0325 AC: 849 AN: 26134

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.0127 AC: 1097 AN: 86258

European-Finnish (FIN) AF: 0.0369 AC: 1973 AN: 53420

Middle Eastern (MID) AF: 0.0166 AC: 96 AN: 5768

European-Non Finnish (NFE) AF: 0.0319 AC: 35477 AN: 1111998

Other (OTH) AF: 0.0254 AC: 1533 AN: 60396

GnomAD4 genome AF: 0.0205 AC: 3118 AN: 152328 Hom.: 50 Cov.: 31 AF XY: 0.0204 AC XY: 1518 AN XY: 74492

African (AFR) AF: 0.00604 AC: 251 AN: 41582

American (AMR) AF: 0.0125 AC: 191 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0372 AC: 129 AN: 3470

East Asian (EAS) AF: 0.000966 AC: 5 AN: 5178

South Asian (SAS) AF: 0.00974 AC: 47 AN: 4826

European-Finnish (FIN) AF: 0.0387 AC: 411 AN: 10620

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0297 AC: 2019 AN: 68024

Other (OTH) AF: 0.0147 AC: 31 AN: 2116

Alfa AF: 0.0263 Hom.: 247

Bravo AF: 0.0185

TwinsUK AF: 0.0316 AC: 117

ALSPAC AF: 0.0350 AC: 135

ESP6500AA AF: 0.00772 AC: 34

ESP6500EA AF: 0.0320 AC: 275

ExAC AF: 0.0212 AC: 2569

Asia WGS AF: 0.00549 AC: 20 AN: 3478

EpiCase AF: 0.0278

EpiControl AF: 0.0285

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	ADIPOQ-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	14
DANN	Benign	0.92
DEOGEN2	Benign	0.32	T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.44	N
LIST_S2	Benign	0.78	T
MetaRNN	Benign	0.0059	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.3	L
PhyloP100		0.27
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.075
Sift	Benign	0.51	T
Sift4G	Benign	0.54	T
Polyphen		0.0060	B
Vest4		0.032
ClinPred		0.020	T
GERP RS		3.1
Varity_R		0.20
gMVP		0.46
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17366743; hg19: chr3-186572089; COSMIC: COSV99067039;