Variant 10-86970577-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006829.3(ADIRF):c.226A>C(p.Lys76Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000311 in 1,608,204 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ADIRF
NM_006829.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.807

Variant links:

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 links:

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

ADIRF-AS1 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.22168529).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ADIRF	NM_006829.3 linkuse as main transcript	c.226A>C	p.Lys76Gln	missense_variant	3/3	ENST00000372013.8	NP_006820.1
AGAP11	NR_171046.1 linkuse as main transcript	n.242A>C		non_coding_transcript_exon_variant	1/11
ADIRF-AS1	NR_170178.1 linkuse as main transcript	n.185-4T>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ADIRF	ENST00000372013.8 linkuse as main transcript	c.226A>C	p.Lys76Gln	missense_variant	3/3	1	NM_006829.3	ENSP00000361083	P1
ADIRF-AS1	ENST00000418273.2 linkuse as main transcript	n.735T>G		non_coding_transcript_exon_variant	1/3	3
	ENST00000609363.1 linkuse as main transcript	n.125T>G		non_coding_transcript_exon_variant	2/2	4

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151946

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000484

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000122

AC:

AN:

245182

Hom.:

AF XY:

0.00000755

AC XY:

AN XY:

132408

show subpopulations

Gnomad AFR exome

AF:

0.000194

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1456258

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

724174

show subpopulations

Gnomad4 AFR exome

AF:

0.0000900

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151946

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74226

show subpopulations

Gnomad4 AFR

AF:

0.0000484

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 10, 2021

The c.226A>C (p.K76Q) alteration is located in exon 3 (coding exon 3) of the ADIRF gene. This alteration results from a A to C substitution at nucleotide position 226, causing the lysine (K) at amino acid position 76 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.080

Eigen

Benign

-0.057

Eigen_PC

Benign

-0.22

FATHMM_MKL

Benign

0.31

M_CAP

Benign

0.011

MetaRNN

Benign

0.22

MetaSVM

Benign

-0.92

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-2.3

REVEL

Benign

0.062

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.33

MVP

0.014

MPC

0.24

ClinPred

0.88

GERP RS

2.7

Varity_R

0.30

gMVP

0.10

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over