Genetic Variant AAGAB:c.820+158dupA (chr15-67203885-A-AT) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_024666.5(AAGAB):c.820+158dupA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0212 in 148,124 control chromosomes in the GnomAD database, including 61 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.021 ( 61 hom., cov: 32)

Consequence

AAGAB
NM_024666.5 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.230

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

palmoplantar keratoderma, punctate type 1A
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics, Laboratory for Molecular Medicine
punctate palmoplantar keratoderma type 1
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

AAGAB links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 15-67203885-A-AT is Benign according to our data. Variant chr15-67203885-A-AT is described in ClinVar as Benign. ClinVar VariationId is 1183864.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0511 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024666.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
AAGAB	NM_024666.5	MANE Select	c.820+158dupA	intron	N/A	NP_078942.3
AAGAB	NM_001271885.2		c.493+158dupA	intron	N/A	NP_001258814.1	Q6PD74-2
AAGAB	NM_001271886.2		c.493+158dupA	intron	N/A	NP_001258815.1	Q6PD74-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
AAGAB	ENST00000261880.10	TSL:1 MANE Select	c.820+158_820+159insA	intron	N/A	ENSP00000261880.5	Q6PD74-1
AAGAB	ENST00000947778.1		c.868+158_868+159insA	intron	N/A	ENSP00000617837.1
AAGAB	ENST00000902812.1		c.808+158_808+159insA	intron	N/A	ENSP00000572871.1

Frequencies

GnomAD3 genomes

AF:

0.0212

AC:

3143

AN:

148068

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0528

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0143

Gnomad ASJ

AF:

0.00643

Gnomad EAS

AF:

0.00489

Gnomad SAS

AF:

0.0243

Gnomad FIN

AF:

0.00156

Gnomad MID

AF:

0.0194

Gnomad NFE

AF:

0.00857

Gnomad OTH

AF:

0.0168

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.0212

AC:

3147

AN:

148124

Hom.:

Cov.:

AF XY:

0.0209

AC XY:

1511

AN XY:

72184

show subpopulations

African (AFR)

AF:

0.0529

AC:

2154

AN:

40684

American (AMR)

AF:

0.0143

AC:

211

AN:

14798

Ashkenazi Jewish (ASJ)

AF:

0.00643

AC:

AN:

3420

East Asian (EAS)

AF:

0.00491

AC:

AN:

5096

South Asian (SAS)

AF:

0.0235

AC:

110

AN:

4682

European-Finnish (FIN)

AF:

0.00156

AC:

AN:

9614

Middle Eastern (MID)

AF:

0.0210

AC:

AN:

286

European-Non Finnish (NFE)

AF:

0.00856

AC:

570

AN:

66598

Other (OTH)

AF:

0.0166

AC:

AN:

2044

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

146

292

437

583

729

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

160

200

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00122

Hom.:

Bravo

AF:

0.0232

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.23

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over