chr15-67208595-T-C
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_024666.5(AAGAB):c.682A>G(p.Asn228Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00118 in 1,614,174 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0057 ( 6 hom., cov: 33)
Exomes 𝑓: 0.00072 ( 15 hom. )
Consequence
AAGAB
NM_024666.5 missense
NM_024666.5 missense
Scores
18
Clinical Significance
Conservation
PhyloP100: 0.439
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.003647536).
BP6
?
Variant 15-67208595-T-C is Benign according to our data. Variant chr15-67208595-T-C is described in ClinVar as [Benign]. Clinvar id is 776916.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00567 (864/152324) while in subpopulation AFR AF= 0.0196 (816/41574). AF 95% confidence interval is 0.0185. There are 6 homozygotes in gnomad4. There are 402 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High AC in GnomAd at 860 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AAGAB | NM_024666.5 | c.682A>G | p.Asn228Asp | missense_variant | 7/10 | ENST00000261880.10 | |
AAGAB | NM_001271885.2 | c.355A>G | p.Asn119Asp | missense_variant | 7/10 | ||
AAGAB | NM_001271886.2 | c.355A>G | p.Asn119Asp | missense_variant | 7/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AAGAB | ENST00000261880.10 | c.682A>G | p.Asn228Asp | missense_variant | 7/10 | 1 | NM_024666.5 | P1 | |
AAGAB | ENST00000542650.5 | c.355A>G | p.Asn119Asp | missense_variant | 7/10 | 2 | |||
AAGAB | ENST00000561452.5 | c.355A>G | p.Asn119Asp | missense_variant | 7/10 | 5 | |||
AAGAB | ENST00000538028.1 | n.363A>G | non_coding_transcript_exon_variant | 4/7 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00565 AC: 860AN: 152206Hom.: 6 Cov.: 33
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.00140 AC: 350AN: 249538Hom.: 8 AF XY: 0.00108 AC XY: 146AN XY: 135380
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GnomAD4 exome AF: 0.000717 AC: 1048AN: 1461850Hom.: 15 Cov.: 31 AF XY: 0.000638 AC XY: 464AN XY: 727230
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GnomAD4 genome ? AF: 0.00567 AC: 864AN: 152324Hom.: 6 Cov.: 33 AF XY: 0.00540 AC XY: 402AN XY: 74490
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ExAC
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194
Asia WGS
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6
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3478
ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 15, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Benign
T;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;.;T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;.
MutationTaster
Benign
N;N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Benign
T;T;T
Sift4G
Benign
T;T;T
Polyphen
B;.;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at