15-67203885-A-AT

Variant names:

• chr15-67203885-A-AT
• rs111308100
• NM_024666.5:c.820+158dupA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.230
• Publications: 0 publications found

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

ACMG classification

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	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.: 61 Cov.: 32

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.: 61 Cov.: 32 AF XY: 0.0209 AC XY: 1511 AN XY: 72184

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: 22 AN: 3420

East Asian (EAS) AF: 0.00491 AC: 25 AN: 5096

South Asian (SAS) AF: 0.0235 AC: 110 AN: 4682

European-Finnish (FIN) AF: 0.00156 AC: 15 AN: 9614

Middle Eastern (MID) AF: 0.0210 AC: 6 AN: 286

European-Non Finnish (NFE) AF: 0.00856 AC: 570 AN: 66598

Other (OTH) AF: 0.0166 AC: 34 AN: 2044

Alfa AF: 0.00122 Hom.: 0

Bravo AF: 0.0232

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.23
Mutation Taster		=100/0	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs111308100; hg19: chr15-67496223;