NM_024666.5:c.394A>C

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_024666.5(AAGAB):c.394A>C(p.Ile132Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 1,610,922 control chromosomes in the GnomAD database, including 97,347 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.29 ( 7759 hom., cov: 32)

Exomes 𝑓: 0.34 ( 89588 hom. )

Consequence

AAGAB
NM_024666.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 3.02

Variant links:

Genes affected

AAGAB (HGNC:25662): (alpha and gamma adaptin binding protein) The protein encoded by this gene interacts with the gamma-adaptin and alpha-adaptin subunits of complexes involved in clathrin-coated vesicle trafficking. Mutations in this gene are associated with type I punctate palmoplantar keratoderma. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Dec 2012]

AAGAB links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=7.320395E-6).

BP6

Variant 15-67236036-T-G is Benign according to our data. Variant chr15-67236036-T-G is described in ClinVar as [Benign]. Clinvar id is 803103.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-67236036-T-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.641 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AAGAB	NM_024666.5 link	c.394A>C	p.Ile132Leu	missense_variant	Exon 4 of 10	ENST00000261880.10	NP_078942.3	Q6PD74-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AAGAB	ENST00000261880.10 link	c.394A>C	p.Ile132Leu	missense_variant	Exon 4 of 10	1	NM_024666.5	ENSP00000261880.5		Q6PD74-1

Frequencies

GnomAD3 genomes

AF:

0.288

AC:

43822

AN:

151992

Hom.:

7756

Cov.:

show subpopulations

Gnomad AFR

AF:

0.101

Gnomad AMI

AF:

0.260

Gnomad AMR

AF:

0.379

Gnomad ASJ

AF:

0.421

Gnomad EAS

AF:

0.659

Gnomad SAS

AF:

0.457

Gnomad FIN

AF:

0.377

Gnomad MID

AF:

0.369

Gnomad NFE

AF:

0.321

Gnomad OTH

AF:

0.311

GnomAD3 exomes

AF:

0.370

AC:

92019

AN:

248468

Hom.:

18713

AF XY:

0.374

AC XY:

50381

AN XY:

134814

show subpopulations

Gnomad AFR exome

AF:

0.0936

Gnomad AMR exome

AF:

0.407

Gnomad ASJ exome

AF:

0.421

Gnomad EAS exome

AF:

0.665

Gnomad SAS exome

AF:

0.445

Gnomad FIN exome

AF:

0.365

Gnomad NFE exome

AF:

0.327

Gnomad OTH exome

AF:

0.364

GnomAD4 exome

AF:

0.342

AC:

498308

AN:

1458810

Hom.:

89588

Cov.:

AF XY:

0.345

AC XY:

250105

AN XY:

725772

show subpopulations

Gnomad4 AFR exome

AF:

0.0913

Gnomad4 AMR exome

AF:

0.402

Gnomad4 ASJ exome

AF:

0.420

Gnomad4 EAS exome

AF:

0.645

Gnomad4 SAS exome

AF:

0.446

Gnomad4 FIN exome

AF:

0.361

Gnomad4 NFE exome

AF:

0.325

Gnomad4 OTH exome

AF:

0.342

GnomAD4 genome

AF:

0.288

AC:

43837

AN:

152112

Hom.:

7759

Cov.:

AF XY:

0.301

AC XY:

22349

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.100

Gnomad4 AMR

AF:

0.380

Gnomad4 ASJ

AF:

0.421

Gnomad4 EAS

AF:

0.660

Gnomad4 SAS

AF:

0.457

Gnomad4 FIN

AF:

0.377

Gnomad4 NFE

AF:

0.321

Gnomad4 OTH

AF:

0.310

Alfa

AF:

0.328

Hom.:

21564

Bravo

AF:

0.280

TwinsUK

AF:

0.331

AC:

1229

ALSPAC

AF:

0.335

AC:

1291

ESP6500AA

AF:

0.105

AC:

392

ESP6500EA

AF:

0.321

AC:

2639

ExAC

AF:

0.364

AC:

43975

Asia WGS

AF:

0.499

AC:

1734

AN:

3478

EpiCase

AF:

0.336

EpiControl

AF:

0.329

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Palmoplantar keratoderma, punctate type 1A

Benign:2

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 28, 2019

Mendelics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.0035

T;.;.;T

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.054

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.86

D;.;D;D

MetaRNN

Benign

0.0000073

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

L;.;.;.

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.58

N;N;N;N

REVEL

Benign

0.061

Sift

Benign

0.36

T;T;T;T

Sift4G

Benign

0.23

T;T;T;T

Polyphen

0.019

B;.;.;.

Vest4

0.26

MPC

0.080

ClinPred

0.015

GERP RS

5.5

Varity_R

0.21

gMVP

0.39

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