Variant chr20-38581288-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The ENST00000537425.3(ADIG):c.38C>A(p.Thr13Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000417 in 1,461,596 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000042 ( 0 hom. )

Consequence

ADIG
ENST00000537425.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.04

Variant links:

Genes affected

ADIG (HGNC:28606): (adipogenin) ADIG/SMAF1 is an adipocyte-specific protein that plays a role in adipocyte differentiation (Kim et al., 2005 [PubMed 15567149]; Hong et al., 2005 [PubMed 16132694]).[supplied by OMIM, Mar 2008]

ADIG links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.784

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ADIG	NM_001393816.1 linkuse as main transcript	c.38C>A	p.Thr13Lys	missense_variant	1/3	ENST00000537425.3	NP_001380745.1
ADIG	NM_001393817.1 linkuse as main transcript	c.38C>A	p.Thr13Lys	missense_variant	1/3		NP_001380746.1
ADIG	NR_172017.1 linkuse as main transcript	n.92C>A		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ADIG	ENST00000537425.3 linkuse as main transcript	c.38C>A	p.Thr13Lys	missense_variant	1/3	1	NM_001393816.1	ENSP00000440331	P1
ADIG	ENST00000470147.5 linkuse as main transcript	c.38C>A	p.Thr13Lys	missense_variant, NMD_transcript_variant	1/3	1		ENSP00000434385
ADIG	ENST00000416116.2 linkuse as main transcript	c.38C>A	p.Thr13Lys	missense_variant	1/3	3		ENSP00000416834
ADIG	ENST00000373348.4 linkuse as main transcript	c.38C>A	p.Thr13Lys	missense_variant	1/2	2		ENSP00000362445

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249142

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135170

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000885

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000417

AC:

AN:

1461596

Hom.:

Cov.:

AF XY:

0.0000440

AC XY:

AN XY:

727068

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000549

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000282

Hom.:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

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

Dec 28, 2022

The c.38C>A (p.T13K) alteration is located in exon 1 (coding exon 1) of the ADIG gene. This alteration results from a C to A substitution at nucleotide position 38, causing the threonine (T) at amino acid position 13 to be replaced by a lysine (K). 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

Pathogenic

0.42

BayesDel_noAF

Pathogenic

0.36

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.14

T;.

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.71

T;T

M_CAP

Benign

0.081

MetaRNN

Pathogenic

0.78

D;D

MetaSVM

Uncertain

-0.028

MutationTaster

Benign

0.55

D;D

PrimateAI

Uncertain

0.69

PROVEAN

Pathogenic

-6.0

.;D

REVEL

Benign

0.23

Sift

Pathogenic

0.0

.;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;.

Vest4

0.82

MutPred

0.32

Gain of ubiquitination at T13 (P = 0.0192);Gain of ubiquitination at T13 (P = 0.0192);

MVP

0.13

ClinPred

0.99

GERP RS

5.2

Varity_R

0.77

gMVP

0.44

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