chr15-67202485-G-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_024666.5(AAGAB):​c.*336C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AAGAB	NM_024666.5	c.*336C>A		3_prime_UTR_variant	Exon 10 of 10	ENST00000261880.10	NP_078942.3
AAGAB	NM_001271885.2	c.*336C>A		3_prime_UTR_variant	Exon 10 of 10		NP_001258814.1
AAGAB	NM_001271886.2	c.*336C>A		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>A		3_prime_UTR_variant	Exon 10 of 10	1	NM_024666.5	ENSP00000261880.5
AAGAB	ENST00000538028.1	n.965C>A		non_coding_transcript_exon_variant	Exon 7 of 7	2
AAGAB	ENST00000561452.5	c.*336C>A		3_prime_UTR_variant	Exon 10 of 10	5		ENSP00000453263.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 83842 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 43112

African (AFR) AF: 0.00 AC: 0 AN: 3164

American (AMR) AF: 0.00 AC: 0 AN: 4636

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2966

East Asian (EAS) AF: 0.00 AC: 0 AN: 6548

South Asian (SAS) AF: 0.00 AC: 0 AN: 4518

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3646

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 412

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 52662

Other (OTH) AF: 0.00 AC: 0 AN: 5290

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 176

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	11
DANN	Benign	0.82
PhyloP100		0.16
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

Other links and lift over

dbSNP: rs10518716; hg19: chr15-67494823;