Variant 6-143136970-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_016108.4(AIG1):c.277T>G(p.Leu93Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000412 in 1,457,564 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 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 7.7e-7 ( 0 hom. )

Consequence

AIG1
NM_016108.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.188

Variant links:

Genes affected

AIG1 (HGNC:21607): (androgen induced 1) Enables hydrolase activity. Involved in long-chain fatty acid catabolic process. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

AIG1 links:

LOC124901416 (HGNC:):

LOC124901416 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2658661).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AIG1	NM_016108.4 link	c.277T>G	p.Leu93Val	missense_variant	2/6	ENST00000357847.9	NP_057192.2	Q9NVV5-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AIG1	ENST00000357847.9 link	c.277T>G	p.Leu93Val	missense_variant	2/6	1	NM_016108.4	ENSP00000350509.4		Q9NVV5-2

Frequencies

GnomAD3 genomes

AF:

0.0000328

AC:

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

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:

0.0000100

AC:

AN:

199482

Hom.:

AF XY:

0.0000185

AC XY:

AN XY:

108396

show subpopulations

Gnomad AFR exome

AF:

0.000152

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:

7.66e-7

AC:

AN:

1305334

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

639354

show subpopulations

Gnomad4 AFR exome

AF:

0.0000342

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:

0.0000328

AC:

AN:

152230

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.000121

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:

0.0000113

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000247

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

Apr 04, 2024

The c.277T>G (p.L93V) alteration is located in exon 2 (coding exon 2) of the AIG1 gene. This alteration results from a T to G substitution at nucleotide position 277, causing the leucine (L) at amino acid position 93 to be replaced by a valine (V). 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

0.27

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.056

T;.;.;.;.;T;T

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.16

LIST_S2

Uncertain

0.86

D;D;D;D;D;D;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.27

T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.7

.;.;M;M;M;M;.

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-2.3

N;.;N;.;.;N;N

REVEL

Uncertain

0.31

Sift

Uncertain

0.012

D;.;D;.;.;D;D

Sift4G

Uncertain

0.010

D;.;D;D;D;D;T

Polyphen

1.0, 0.76

.;.;D;.;P;.;.

Vest4

0.45, 0.48, 0.47, 0.49

MVP

0.085

MPC

0.80

ClinPred

0.73

GERP RS

-4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.15

gMVP

0.44

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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