Variant 20-38581364-A-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 ENST00000537425.3(ADIG):c.114A>T(p.Leu38Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,613,958 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: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ADIG
ENST00000537425.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.479

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14131987).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ADIG	NM_001393816.1 linkuse as main transcript	c.114A>T	p.Leu38Phe	missense_variant	1/3	ENST00000537425.3	NP_001380745.1
ADIG	NM_001393817.1 linkuse as main transcript	c.114A>T	p.Leu38Phe	missense_variant	1/3		NP_001380746.1
ADIG	NR_172017.1 linkuse as main transcript	n.168A>T		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.114A>T	p.Leu38Phe	missense_variant	1/3	1	NM_001393816.1	ENSP00000440331	P1
ADIG	ENST00000470147.5 linkuse as main transcript	c.114A>T	p.Leu38Phe	missense_variant, NMD_transcript_variant	1/3	1		ENSP00000434385
ADIG	ENST00000416116.2 linkuse as main transcript	c.114A>T	p.Leu38Phe	missense_variant	1/3	3		ENSP00000416834
ADIG	ENST00000373348.4 linkuse as main transcript	c.114A>T	p.Leu38Phe	missense_variant	1/2	2		ENSP00000362445

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

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

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461656

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727104

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:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152302

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Asia WGS

AF:

0.000289

AC:

AN:

3478

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 21, 2023

The c.114A>T (p.L38F) alteration is located in exon 1 (coding exon 1) of the ADIG gene. This alteration results from a A to T substitution at nucleotide position 114, causing the leucine (L) at amino acid position 38 to be replaced by a phenylalanine (F). 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

0.26

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Uncertain

-0.060

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

T;.

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.29

FATHMM_MKL

Benign

0.32

LIST_S2

Benign

0.70

T;T

M_CAP

Benign

0.049

MetaRNN

Benign

0.14

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.95

N;N

PrimateAI

Benign

0.47

PROVEAN

Uncertain

-4.0

.;D

REVEL

Benign

0.22

Sift

Pathogenic

0.0

.;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.56

P;.

Vest4

0.38

MutPred

0.25

Loss of catalytic residue at L38 (P = 0.081);Loss of catalytic residue at L38 (P = 0.081);

MVP

0.048

ClinPred

0.96

GERP RS

-3.5

Varity_R

0.13

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