15-67202584-T-C

Variant names:

• chr15-67202584-T-C
• rs12148121
• NM_024666.5:c.*237A>G

Variant summary

Our verdict is Benign. The variant received -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
• 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]

AAGAB Gene-Disease associations (from GenCC):

• palmoplantar keratoderma, punctate type 1A

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

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024666.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AAGAB	NM_024666.5	MANE Select	c.*237A>G		3_prime_UTR	Exon 10 of 10	NP_078942.3
	AAGAB	NM_001271885.2		c.*237A>G		3_prime_UTR	Exon 10 of 10	NP_001258814.1	Q6PD74-2
	AAGAB	NM_001271886.2		c.*237A>G		3_prime_UTR	Exon 10 of 10	NP_001258815.1	Q6PD74-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AAGAB	ENST00000261880.10	TSL:1 MANE Select	c.*237A>G		3_prime_UTR	Exon 10 of 10	ENSP00000261880.5	Q6PD74-1
	AAGAB	ENST00000947778.1		c.*237A>G		3_prime_UTR	Exon 11 of 11	ENSP00000617837.1
	AAGAB	ENST00000902812.1		c.*237A>G		3_prime_UTR	Exon 10 of 10	ENSP00000572871.1

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

African (AFR) AF: 0.0617 AC: 657 AN: 10648

American (AMR) AF: 0.338 AC: 4531 AN: 13392

Ashkenazi Jewish (ASJ) AF: 0.362 AC: 3963 AN: 10962

East Asian (EAS) AF: 0.484 AC: 12983 AN: 26832

South Asian (SAS) AF: 0.298 AC: 6468 AN: 21732

European-Finnish (FIN) AF: 0.172 AC: 3865 AN: 22514

Middle Eastern (MID) AF: 0.321 AC: 492 AN: 1534

European-Non Finnish (NFE) AF: 0.230 AC: 47187 AN: 205026

Other (OTH) AF: 0.243 AC: 4901 AN: 20170

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

African (AFR) AF: 0.0598 AC: 2485 AN: 41540

American (AMR) AF: 0.320 AC: 4889 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.364 AC: 1263 AN: 3466

East Asian (EAS) AF: 0.467 AC: 2422 AN: 5184

South Asian (SAS) AF: 0.298 AC: 1434 AN: 4814

European-Finnish (FIN) AF: 0.181 AC: 1918 AN: 10582

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

European-Non Finnish (NFE) AF: 0.229 AC: 15550 AN: 67986

Other (OTH) AF: 0.241 AC: 508 AN: 2112

Alfa AF: 0.216 Hom.: 809

Bravo AF: 0.207

Asia WGS AF: 0.342 AC: 1191 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.59
DANN	Benign	0.75
PhyloP100		0.052
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
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: rs12148121; hg19: chr15-67494922;