rs10518716

Positions:

• chr15-67202485-G-C
• chr15-67202485-G-T

Variant summary

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

The NM_024666.5(AAGAB):​c.*336C>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 0.229 in 235,686 control chromosomes in the GnomAD database, including 7,325 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 (4128 hom., cov: 32)
  • Exomes 𝑓: 0.26 (3197 hom.)
• Consequence: AAGAB NM_024666.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.163

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=-0.79).
• 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	UniProt
AAGAB	NM_024666.5	c.*336C>G		3_prime_UTR_variant	10/10	ENST00000261880.10
AAGAB	NM_001271885.2	c.*336C>G		3_prime_UTR_variant	10/10
AAGAB	NM_001271886.2	c.*336C>G		3_prime_UTR_variant	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AAGAB	ENST00000261880.10	c.*336C>G		3_prime_UTR_variant	10/10	1	NM_024666.5	P1
AAGAB	ENST00000561452.5	c.*336C>G		3_prime_UTR_variant	10/10	5
AAGAB	ENST00000538028.1	n.965C>G		non_coding_transcript_exon_variant	7/7	2

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32436 AN: 151960 Hom.: 4123 Cov.: 32

Gnomad AFR AF: 0.0993

Gnomad AMI AF: 0.211

Gnomad AMR AF: 0.323

Gnomad ASJ AF: 0.364

Gnomad EAS AF: 0.470

Gnomad SAS AF: 0.300

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.247

GnomAD4 exome AF: 0.257 AC: 21496 AN: 83608 Hom.: 3197 Cov.: 0 AF XY: 0.258 AC XY: 11077 AN XY: 43000

Gnomad4 AFR exome AF: 0.103

Gnomad4 AMR exome AF: 0.325

Gnomad4 ASJ exome AF: 0.356

Gnomad4 EAS exome AF: 0.485

Gnomad4 SAS exome AF: 0.293

Gnomad4 FIN exome AF: 0.167

Gnomad4 NFE exome AF: 0.231

Gnomad4 OTH exome AF: 0.242

GnomAD4 genome AF: 0.214 AC: 32470 AN: 152078 Hom.: 4128 Cov.: 32 AF XY: 0.218 AC XY: 16202 AN XY: 74336

Gnomad4 AFR AF: 0.0995

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: 0.229

Gnomad4 OTH AF: 0.249

Alfa AF: 0.113 Hom.: 176

Bravo AF: 0.220

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	11
DANN	Benign	0.83
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs10518716; hg19: chr15-67494823;