chr10-86970218-C-T

Variant names:

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

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>T​(p.Ala27Val) 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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A27P) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ADIRF NM_006829.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.94
• Publications: 1 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=0.11775732).

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>T	p.Ala27Val	missense	Exon 2 of 3	NP_006820.1	Q15847
	ADIRF-AS1	NR_170181.1		n.574G>A		non_coding_transcript_exon	Exon 2 of 3
	ADIRF-AS1	NR_170182.1		n.574G>A		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>T	p.Ala27Val	missense	Exon 2 of 3	ENSP00000361083.3	Q15847
	ADIRF	ENST00000953690.1		c.74C>T	p.Ala25Val	missense	Exon 2 of 3	ENSP00000623749.1
	ADIRF	ENST00000416348.1	TSL:2	c.62-258C>T		intron	N/A	ENSP00000394643.1	Q5TBU2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00 AC: 0 AN: 93658 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1303922 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 631422

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: 0.00 AC: 0 AN: 1033272

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

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	16
DANN	Benign	0.92
DEOGEN2	Benign	0.092	T
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.22	N
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.97	T
PhyloP100		1.9
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.15
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.040	D
Polyphen		0.25	B
Vest4		0.35
MutPred		0.25		Loss of glycosylation at S22 (P = 0.1486)
MVP		0.014
MPC		0.040
ClinPred		0.20	T
GERP RS		1.9
Varity_R		0.079
gMVP		0.086
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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;