rs10518716

Variant names:

• chr15-67202485-G-C
• rs10518716
• NM_024666.5:c.*336C>G

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 21 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]

AAGAB Gene-Disease associations (from GenCC):

• palmoplantar keratoderma, punctate type 1A

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Ambry Genetics, Laboratory for Molecular Medicine, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• punctate palmoplantar keratoderma type 1

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
AAGAB	NM_024666.5	c.*336C>G		3_prime_UTR_variant	Exon 10 of 10	ENST00000261880.10	NP_078942.3
AAGAB	NM_001271885.2	c.*336C>G		3_prime_UTR_variant	Exon 10 of 10		NP_001258814.1
AAGAB	NM_001271886.2	c.*336C>G		3_prime_UTR_variant	Exon 10 of 10		NP_001258815.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AAGAB	ENST00000261880.10	c.*336C>G		3_prime_UTR_variant	Exon 10 of 10	1	NM_024666.5	ENSP00000261880.5
AAGAB	ENST00000538028.1	n.965C>G		non_coding_transcript_exon_variant	Exon 7 of 7	2
AAGAB	ENST00000561452.5	c.*336C>G		3_prime_UTR_variant	Exon 10 of 10	5		ENSP00000453263.1

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

African (AFR) AF: 0.103 AC: 324 AN: 3160

American (AMR) AF: 0.325 AC: 1502 AN: 4624

Ashkenazi Jewish (ASJ) AF: 0.356 AC: 1049 AN: 2948

East Asian (EAS) AF: 0.485 AC: 3161 AN: 6522

South Asian (SAS) AF: 0.293 AC: 1319 AN: 4504

European-Finnish (FIN) AF: 0.167 AC: 609 AN: 3640

Middle Eastern (MID) AF: 0.338 AC: 138 AN: 408

European-Non Finnish (NFE) AF: 0.231 AC: 12119 AN: 52526

Other (OTH) AF: 0.242 AC: 1275 AN: 5276

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

African (AFR) AF: 0.0995 AC: 4129 AN: 41496

American (AMR) AF: 0.323 AC: 4938 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.364 AC: 1263 AN: 3468

East Asian (EAS) AF: 0.471 AC: 2426 AN: 5154

South Asian (SAS) AF: 0.299 AC: 1443 AN: 4822

European-Finnish (FIN) AF: 0.181 AC: 1918 AN: 10578

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.229 AC: 15541 AN: 67970

Other (OTH) AF: 0.249 AC: 526 AN: 2112

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
PhyloP100		0.16
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs10518716; hg19: chr15-67494823;