Variant chr15-67208695-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_024666.5(AAGAB):c.619-37C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 1,577,086 control chromosomes in the GnomAD database, including 49,482 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 4063 hom., cov: 32)

Exomes 𝑓: 0.24 ( 45419 hom. )

Consequence

AAGAB
NM_024666.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.184

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 15-67208695-G-A is Benign according to our data. Variant chr15-67208695-G-A is described in ClinVar as [Benign]. Clinvar id is 1257765.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
AAGAB	NM_024666.5 linkuse as main transcript	c.619-37C>T	intron_variant	ENST00000261880.10
AAGAB	NM_001271885.2 linkuse as main transcript	c.292-37C>T	intron_variant
AAGAB	NM_001271886.2 linkuse as main transcript	c.292-37C>T	intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
AAGAB	ENST00000261880.10 linkuse as main transcript	c.619-37C>T	intron_variant	1	NM_024666.5	P1	Q6PD74-1
AAGAB	ENST00000542650.5 linkuse as main transcript	c.292-37C>T	intron_variant	2			Q6PD74-2
AAGAB	ENST00000561452.5 linkuse as main transcript	c.292-37C>T	intron_variant	5			Q6PD74-2
AAGAB	ENST00000538028.1 linkuse as main transcript	n.300-37C>T	intron_variant, non_coding_transcript_variant	2

Frequencies

GnomAD3 genomes

AF:

0.209

AC:

31782

AN:

151906

Hom.:

4061

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0841

Gnomad AMI

AF:

0.212

Gnomad AMR

AF:

0.322

Gnomad ASJ

AF:

0.365

Gnomad EAS

AF:

0.470

Gnomad SAS

AF:

0.299

Gnomad FIN

AF:

0.182

Gnomad MID

AF:

0.320

Gnomad NFE

AF:

0.228

Gnomad OTH

AF:

0.245

GnomAD3 exomes

AF:

0.270

AC:

66286

AN:

245194

Hom.:

10025

AF XY:

0.270

AC XY:

35852

AN XY:

133002

show subpopulations

Gnomad AFR exome

AF:

0.0789

Gnomad AMR exome

AF:

0.372

Gnomad ASJ exome

AF:

0.364

Gnomad EAS exome

AF:

0.482

Gnomad SAS exome

AF:

0.293

Gnomad FIN exome

AF:

0.176

Gnomad NFE exome

AF:

0.236

Gnomad OTH exome

AF:

0.266

GnomAD4 exome

AF:

0.244

AC:

347909

AN:

1425062

Hom.:

45419

Cov.:

AF XY:

0.246

AC XY:

174620

AN XY:

710948

show subpopulations

Gnomad4 AFR exome

AF:

0.0791

Gnomad4 AMR exome

AF:

0.365

Gnomad4 ASJ exome

AF:

0.364

Gnomad4 EAS exome

AF:

0.487

Gnomad4 SAS exome

AF:

0.297

Gnomad4 FIN exome

AF:

0.174

Gnomad4 NFE exome

AF:

0.231

Gnomad4 OTH exome

AF:

0.248

GnomAD4 genome

AF:

0.209

AC:

31803

AN:

152024

Hom.:

4063

Cov.:

AF XY:

0.214

AC XY:

15893

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.0840

Gnomad4 AMR

AF:

0.322

Gnomad4 ASJ

AF:

0.365

Gnomad4 EAS

AF:

0.471

Gnomad4 SAS

AF:

0.298

Gnomad4 FIN

AF:

0.182

Gnomad4 NFE

AF:

0.228

Gnomad4 OTH

AF:

0.247

Alfa

AF:

0.232

Hom.:

1190

Bravo

AF:

0.215

Asia WGS

AF:

0.354

AC:

1231

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -

Palmoplantar keratoderma, punctate type 1A

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

8.9

DANN

Benign

0.34

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