15-67232612-T-C

Variant names:

• chr15-67232612-T-C
• rs1822829
• NM_024666.5:c.452-715A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_024666.5(AAGAB):​c.452-715A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 377,674 control chromosomes in the GnomAD database, including 33,580 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 0.45 (15946 hom., cov: 32)
  • Exomes 𝑓: 0.37 (17634 hom.)
• Consequence: AAGAB NM_024666.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.94
• Publications: 10 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]

RPS24P16 (HGNC:35542): (ribosomal protein S24 pseudogene 16)

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.516 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AAGAB	NM_024666.5	c.452-715A>G		intron_variant	Intron 4 of 9	ENST00000261880.10	NP_078942.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AAGAB	ENST00000261880.10	c.452-715A>G		intron_variant	Intron 4 of 9	1	NM_024666.5	ENSP00000261880.5

Frequencies

GnomAD3 genomes AF: 0.451 AC: 68596 AN: 151962 Hom.: 15945 Cov.: 32

Gnomad AFR AF: 0.407

Gnomad AMI AF: 0.475

Gnomad AMR AF: 0.347

Gnomad ASJ AF: 0.419

Gnomad EAS AF: 0.193

Gnomad SAS AF: 0.324

Gnomad FIN AF: 0.526

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.521

Gnomad OTH AF: 0.434

GnomAD4 exome AF: 0.372 AC: 83971 AN: 225594 Hom.: 17634 Cov.: 0 AF XY: 0.371 AC XY: 48449 AN XY: 130696

African (AFR) AF: 0.323 AC: 1930 AN: 5982

American (AMR) AF: 0.194 AC: 5138 AN: 26436

Ashkenazi Jewish (ASJ) AF: 0.344 AC: 2434 AN: 7078

East Asian (EAS) AF: 0.130 AC: 1210 AN: 9340

South Asian (SAS) AF: 0.266 AC: 10337 AN: 38872

European-Finnish (FIN) AF: 0.492 AC: 5412 AN: 10992

Middle Eastern (MID) AF: 0.391 AC: 290 AN: 742

European-Non Finnish (NFE) AF: 0.458 AC: 53026 AN: 115852

Other (OTH) AF: 0.407 AC: 4194 AN: 10300

GnomAD4 genome AF: 0.451 AC: 68609 AN: 152080 Hom.: 15946 Cov.: 32 AF XY: 0.446 AC XY: 33168 AN XY: 74366

African (AFR) AF: 0.407 AC: 16871 AN: 41460

American (AMR) AF: 0.346 AC: 5284 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.419 AC: 1453 AN: 3470

East Asian (EAS) AF: 0.193 AC: 999 AN: 5184

South Asian (SAS) AF: 0.325 AC: 1566 AN: 4818

European-Finnish (FIN) AF: 0.526 AC: 5555 AN: 10566

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.521 AC: 35397 AN: 67984

Other (OTH) AF: 0.429 AC: 905 AN: 2112

Alfa AF: 0.452 Hom.: 2775

Bravo AF: 0.434

Asia WGS AF: 0.253 AC: 881 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	12
DANN	Benign	0.85
PhyloP100		2.9
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1822829; hg19: chr15-67524950;