Variant 15-67204120-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_024666.5(AAGAB):c.744A>T(p.Glu248Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00014 in 1,610,656 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 Benign (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

AAGAB
NM_024666.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.62

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.03526506).

BP6

Variant 15-67204120-T-A is Benign according to our data. Variant chr15-67204120-T-A is described in ClinVar as [Benign]. Clinvar id is 2763265.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.000137 (200/1458436) while in subpopulation AMR AF= 0.000382 (17/44520). AF 95% confidence interval is 0.000243. There are 0 homozygotes in gnomad4_exome. There are 97 alleles in male gnomad4_exome subpopulation. Median coverage is 29. This position pass quality control queck.

BS2

High AC in GnomAd4 at 26 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
AAGAB	NM_024666.5 linkuse as main transcript	c.744A>T	p.Glu248Asp	missense_variant	8/10	ENST00000261880.10
AAGAB	NM_001271885.2 linkuse as main transcript	c.417A>T	p.Glu139Asp	missense_variant	8/10
AAGAB	NM_001271886.2 linkuse as main transcript	c.417A>T	p.Glu139Asp	missense_variant	8/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AAGAB	ENST00000261880.10 linkuse as main transcript	c.744A>T	p.Glu248Asp	missense_variant	8/10	1	NM_024666.5	P1	Q6PD74-1
AAGAB	ENST00000542650.5 linkuse as main transcript	c.417A>T	p.Glu139Asp	missense_variant	8/10	2			Q6PD74-2
AAGAB	ENST00000561452.5 linkuse as main transcript	c.417A>T	p.Glu139Asp	missense_variant	8/10	5			Q6PD74-2
AAGAB	ENST00000538028.1 linkuse as main transcript	n.425A>T		non_coding_transcript_exon_variant	5/7	2

Frequencies

GnomAD3 genomes

AF:

0.000171

AC:

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00490

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000278

AC:

AN:

248448

Hom.:

AF XY:

0.000230

AC XY:

AN XY:

134790

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000526

Gnomad ASJ exome

AF:

0.00428

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000620

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.000137

AC:

200

AN:

1458436

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

725704

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

Gnomad4 AMR exome

AF:

0.000382

Gnomad4 ASJ exome

AF:

0.00445

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000343

Gnomad4 OTH exome

AF:

0.000464

GnomAD4 genome

AF:

0.000171

AC:

AN:

152220

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00490

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000540

Hom.:

Bravo

AF:

0.000185

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000121

AC:

ExAC

AF:

0.000257

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Mar 23, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.57

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0019

T;.;.

Eigen

Uncertain

0.19

Eigen_PC

Benign

0.14

FATHMM_MKL

Uncertain

0.79

LIST_S2

Uncertain

0.93

D;.;D

M_CAP

Benign

0.018

MetaRNN

Benign

0.035

T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Uncertain

2.3

M;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-0.50

N;N;N

REVEL

Benign

0.18

Sift

Pathogenic

0.0

D;T;T

Sift4G

Benign

0.20

T;D;D

Polyphen

1.0

D;.;.

Vest4

0.65

MutPred

0.59

Gain of disorder (P = 0.1976);.;.;

MVP

0.20

MPC

0.082

ClinPred

0.11

GERP RS

1.7

Varity_R

0.39

gMVP

0.29

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