15-67208695-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.184

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 -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	HGVSp	Effect	#exon/exons	MANE	UniProt
AAGAB	NM_024666.5	c.619-37C>T		intron_variant		ENST00000261880.10
AAGAB	NM_001271885.2	c.292-37C>T		intron_variant
AAGAB	NM_001271886.2	c.292-37C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AAGAB	ENST00000261880.10	c.619-37C>T		intron_variant		1	NM_024666.5	P1
AAGAB	ENST00000542650.5	c.292-37C>T		intron_variant		2
AAGAB	ENST00000561452.5	c.292-37C>T		intron_variant		5
AAGAB	ENST00000538028.1	n.300-37C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31782 AN: 151906 Hom.: 4061 Cov.: 32

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

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.: 24 AF XY: 0.246 AC XY: 174620 AN XY: 710948

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.: 32 AF XY: 0.214 AC XY: 15893 AN XY: 74302

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Palmoplantar keratoderma, punctate type 1A Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

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

Other links and lift over

dbSNP: rs2289262; hg19: chr15-67501033;