Variant 10-86968587-G-T 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.43G>T(p.Gly15Trp) 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 1,461,052 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ADIRF
NM_006829.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.04

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:

MMRN2 (HGNC:19888): (multimerin 2) This gene encodes a protein belonging to the member of elastin microfibril interface-located (EMILIN) protein family. This family member is an extracellular matrix glycoprotein that can interfere with tumor angiogenesis and growth. It serves as a transforming growth factor beta antagonist and can interfere with the VEGF-A/VEGFR2 pathway. A related pseudogene has been identified on chromosome 6. [provided by RefSeq, Aug 2012]

MMRN2 links:

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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=0.21322948).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADIRF	NM_006829.3 linkuse as main transcript	c.43G>T	p.Gly15Trp	missense_variant	1/3	ENST00000372013.8	NP_006820.1
ADIRF-AS1	NR_170178.1 linkuse as main transcript	n.1136+469C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADIRF	ENST00000372013.8 linkuse as main transcript	c.43G>T	p.Gly15Trp	missense_variant	1/3	1	NM_006829.3	ENSP00000361083	P1
ADIRF-AS1	ENST00000418273.2 linkuse as main transcript	n.2129+455C>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249270

Hom.:

AF XY:

0.00000740

AC XY:

AN XY:

135202

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000547

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:

6.84e-7

AC:

AN:

1461052

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726832

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

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

Cov.:

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 04, 2023

The c.43G>T (p.G15W) alteration is located in exon 1 (coding exon 1) of the ADIRF gene. This alteration results from a G to T substitution at nucleotide position 43, causing the glycine (G) at amino acid position 15 to be replaced by a tryptophan (W). 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

Pathogenic

0.58

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.22

CADD

Pathogenic

DANN

Benign

0.96

DEOGEN2

Benign

0.25

T;T

Eigen

Uncertain

0.21

Eigen_PC

Benign

0.081

FATHMM_MKL

Benign

0.65

LIST_S2

Benign

0.53

.;T

M_CAP

Benign

0.046

MetaRNN

Benign

0.21

T;T

MetaSVM

Benign

-0.83

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.56

PROVEAN

Pathogenic

-5.7

D;D

REVEL

Benign

0.21

Sift

Uncertain

0.011

D;.

Sift4G

Uncertain

0.033

D;D

Polyphen

1.0

D;.

Vest4

0.42

MutPred

0.28

Gain of MoRF binding (P = 0.0298);Gain of MoRF binding (P = 0.0298);

MVP

0.092

MPC

0.23

ClinPred

0.86

GERP RS

4.4

Varity_R

0.27

gMVP

0.11

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.17

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