chr15-67202584-T-C

Position:

• chr15-67202584-T-C

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.*237A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 484,966 control chromosomes in the GnomAD database, including 16,598 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3965 hom., cov: 32)
  • Exomes 𝑓: 0.26 (12633 hom.)
• Consequence: AAGAB NM_024666.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0520

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=-0.85).
• BP6: Variant 15-67202584-T-C is Benign according to our data. Variant chr15-67202584-T-C is described in ClinVar as [Benign]. Clinvar id is 1283054.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AAGAB	NM_024666.5	c.*237A>G		3_prime_UTR_variant	10/10	ENST00000261880.10
AAGAB	NM_001271885.2	c.*237A>G		3_prime_UTR_variant	10/10
AAGAB	NM_001271886.2	c.*237A>G		3_prime_UTR_variant	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AAGAB	ENST00000261880.10	c.*237A>G		3_prime_UTR_variant	10/10	1	NM_024666.5	P1
AAGAB	ENST00000561452.5	c.*237A>G		3_prime_UTR_variant	10/10	5
AAGAB	ENST00000538028.1	n.866A>G		non_coding_transcript_exon_variant	7/7	2

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30744 AN: 152038 Hom.: 3963 Cov.: 32

Gnomad AFR AF: 0.0600

Gnomad AMI AF: 0.211

Gnomad AMR AF: 0.319

Gnomad ASJ AF: 0.364

Gnomad EAS AF: 0.466

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.240

GnomAD4 exome AF: 0.256 AC: 85047 AN: 332810 Hom.: 12633 Cov.: 2 AF XY: 0.257 AC XY: 44275 AN XY: 172194

Gnomad4 AFR exome AF: 0.0617

Gnomad4 AMR exome AF: 0.338

Gnomad4 ASJ exome AF: 0.362

Gnomad4 EAS exome AF: 0.484

Gnomad4 SAS exome AF: 0.298

Gnomad4 FIN exome AF: 0.172

Gnomad4 NFE exome AF: 0.230

Gnomad4 OTH exome AF: 0.243

GnomAD4 genome AF: 0.202 AC: 30755 AN: 152156 Hom.: 3965 Cov.: 32 AF XY: 0.207 AC XY: 15381 AN XY: 74380

Gnomad4 AFR AF: 0.0598

Gnomad4 AMR AF: 0.320

Gnomad4 ASJ AF: 0.364

Gnomad4 EAS AF: 0.467

Gnomad4 SAS AF: 0.298

Gnomad4 FIN AF: 0.181

Gnomad4 NFE AF: 0.229

Gnomad4 OTH AF: 0.241

Alfa AF: 0.219 Hom.: 804

Bravo AF: 0.207

Asia WGS AF: 0.342 AC: 1191 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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	Jun 18, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.59
DANN	Benign	0.75
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1

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: rs12148121; hg19: chr15-67494922;