15-67228279-T-C

Position:

• chr15-67228279-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024666.5(AAGAB):​c.535+3535A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 152,216 control chromosomes in the GnomAD database, including 4,130 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.21 (4130 hom., cov: 33)
• Consequence: AAGAB NM_024666.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.450

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.455 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AAGAB	NM_024666.5	c.535+3535A>G		intron_variant		ENST00000261880.10	NP_078942.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AAGAB	ENST00000261880.10	c.535+3535A>G		intron_variant		1	NM_024666.5	ENSP00000261880	P1
AAGAB	ENST00000542650.5	c.208+3535A>G		intron_variant		2		ENSP00000440735
AAGAB	ENST00000561452.5	c.208+3535A>G		intron_variant		5		ENSP00000453263
AAGAB	ENST00000558725.5	n.559-1329A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32478 AN: 152098 Hom.: 4125 Cov.: 33

Gnomad AFR AF: 0.100

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.322

Gnomad ASJ AF: 0.364

Gnomad EAS AF: 0.470

Gnomad SAS AF: 0.299

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.228

Gnomad OTH AF: 0.247

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

GnomAD4 genome AF: 0.214 AC: 32512 AN: 152216 Hom.: 4130 Cov.: 33 AF XY: 0.218 AC XY: 16235 AN XY: 74428

Gnomad4 AFR AF: 0.100

Gnomad4 AMR AF: 0.323

Gnomad4 ASJ AF: 0.364

Gnomad4 EAS AF: 0.471

Gnomad4 SAS AF: 0.299

Gnomad4 FIN AF: 0.181

Gnomad4 NFE AF: 0.228

Gnomad4 OTH AF: 0.249

Alfa AF: 0.112 Hom.: 176

Bravo AF: 0.220

Asia WGS AF: 0.359 AC: 1248 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	15
DANN	Benign	0.79

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: rs4776906; hg19: chr15-67520617;