15-67203885-A-AT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_024666.5(AAGAB):c.820+158_820+159insA 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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AAGAB	NM_024666.5	c.820+158_820+159insA		intron_variant		ENST00000261880.10
AAGAB	NM_001271885.2	c.493+158_493+159insA		intron_variant
AAGAB	NM_001271886.2	c.493+158_493+159insA		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AAGAB	ENST00000261880.10	c.820+158_820+159insA		intron_variant		1	NM_024666.5	P1
AAGAB	ENST00000542650.5	c.493+158_493+159insA		intron_variant		2
AAGAB	ENST00000561452.5	c.493+158_493+159insA		intron_variant		5
AAGAB	ENST00000538028.1	n.501+158_501+159insA		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR AF: 0.0529

Gnomad4 AMR AF: 0.0143

Gnomad4 ASJ AF: 0.00643

Gnomad4 EAS AF: 0.00491

Gnomad4 SAS AF: 0.0235

Gnomad4 FIN AF: 0.00156

Gnomad4 NFE AF: 0.00856

Gnomad4 OTH AF: 0.0166

Bravo AF: 0.0232

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 18, 2021

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs111308100; hg19: chr15-67496223;