10-86970218-C-G

Variant names:

• chr10-86970218-C-G
• rs1365784716
• NM_006829.3:c.80C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006829.3(ADIRF):​c.80C>G​(p.Ala27Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000767 in 1,303,920 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict 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. A27V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.7e-7 (0 hom.)
• Consequence: ADIRF NM_006829.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.94
• Publications: 0 publications found

Genes affected

ADIRF (HGNC:24043): (adipogenesis regulatory factor) APM2 gene is exclusively expressed in adipose tissue. Its function is currently unknown. [provided by RefSeq, Jul 2008]

ADIRF-AS1 (HGNC:45127): (ADIRF antisense RNA 1)

ENSG00000293605 (HGNC:):

AGAP11 (HGNC:29421): (ArfGAP with GTPase domain, ankyrin repeat and PH domain 11) Predicted to enable GTPase activator activity and metal ion binding activity. Predicted to be involved in regulation of catalytic activity. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.115284085).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006829.3. 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
	ADIRF	NM_006829.3	MANE Select	c.80C>G	p.Ala27Gly	missense	Exon 2 of 3	NP_006820.1	Q15847
	ADIRF-AS1	NR_170181.1		n.574G>C		non_coding_transcript_exon	Exon 2 of 3
	ADIRF-AS1	NR_170182.1		n.574G>C		non_coding_transcript_exon	Exon 2 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADIRF	ENST00000372013.8	TSL:1 MANE Select	c.80C>G	p.Ala27Gly	missense	Exon 2 of 3	ENSP00000361083.3	Q15847
	ADIRF	ENST00000953690.1		c.74C>G	p.Ala25Gly	missense	Exon 2 of 3	ENSP00000623749.1
	ADIRF	ENST00000416348.1	TSL:2	c.62-258C>G		intron	N/A	ENSP00000394643.1	Q5TBU2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.67e-7 AC: 1 AN: 1303920 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 631420

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 28680

American (AMR) AF: 0.00 AC: 0 AN: 20926

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18918

East Asian (EAS) AF: 0.00 AC: 0 AN: 35232

South Asian (SAS) AF: 0.00 AC: 0 AN: 62180

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45822

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5102

European-Non Finnish (NFE) AF: 9.68e-7 AC: 1 AN: 1033270

Other (OTH) AF: 0.00 AC: 0 AN: 53790

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	17
DANN	Benign	0.82
DEOGEN2	Benign	0.27	T
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.23	N
M_CAP	Benign	0.0090	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.97	T
PhyloP100		1.9
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.071
Sift	Uncertain	0.027	D
Sift4G	Uncertain	0.059	T
Polyphen		0.12	B
Vest4		0.30
MutPred		0.20		Gain of loop (P = 0.002)
MVP		0.014
MPC		0.041
ClinPred		0.075	T
GERP RS		1.9
Varity_R		0.11
gMVP		0.083
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1365784716; hg19: chr10-88729975;