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GeneBe

15-67208608-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_024666.5(AAGAB):c.669G>A(p.Arg223=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00125 in 1,614,130 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0016 ( 3 hom., cov: 33)
Exomes 𝑓: 0.0012 ( 15 hom. )

Consequence

AAGAB
NM_024666.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0470
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.73).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 15-67208608-C-T is Benign according to our data. Variant chr15-67208608-C-T is described in ClinVar as [Benign]. Clinvar id is 769885.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.047 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00163 (248/152262) while in subpopulation EAS AF= 0.0347 (180/5194). AF 95% confidence interval is 0.0305. There are 3 homozygotes in gnomad4. There are 148 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 247 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
AAGABNM_024666.5 linkuse as main transcriptc.669G>A p.Arg223= synonymous_variant 7/10 ENST00000261880.10
AAGABNM_001271885.2 linkuse as main transcriptc.342G>A p.Arg114= synonymous_variant 7/10
AAGABNM_001271886.2 linkuse as main transcriptc.342G>A p.Arg114= synonymous_variant 7/10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
AAGABENST00000261880.10 linkuse as main transcriptc.669G>A p.Arg223= synonymous_variant 7/101 NM_024666.5 P1Q6PD74-1
AAGABENST00000542650.5 linkuse as main transcriptc.342G>A p.Arg114= synonymous_variant 7/102 Q6PD74-2
AAGABENST00000561452.5 linkuse as main transcriptc.342G>A p.Arg114= synonymous_variant 7/105 Q6PD74-2
AAGABENST00000538028.1 linkuse as main transcriptn.350G>A non_coding_transcript_exon_variant 4/72

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00162
AC:
247
AN:
152144
Hom.:
3
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000965
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00151
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.0344
Gnomad SAS
AF:
0.00311
Gnomad FIN
AF:
0.00141
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000118
Gnomad OTH
AF:
0.00143
GnomAD3 exomes
AF:
0.00346
AC:
863
AN:
249552
Hom.:
7
AF XY:
0.00311
AC XY:
421
AN XY:
135388
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00492
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0318
Gnomad SAS exome
AF:
0.00105
Gnomad FIN exome
AF:
0.00227
Gnomad NFE exome
AF:
0.000230
Gnomad OTH exome
AF:
0.00231
GnomAD4 exome
AF:
0.00121
AC:
1769
AN:
1461868
Hom.:
15
Cov.:
30
AF XY:
0.00120
AC XY:
870
AN XY:
727230
show subpopulations
Gnomad4 AFR exome
AF:
0.0000896
Gnomad4 AMR exome
AF:
0.00434
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0278
Gnomad4 SAS exome
AF:
0.00102
Gnomad4 FIN exome
AF:
0.00217
Gnomad4 NFE exome
AF:
0.000119
Gnomad4 OTH exome
AF:
0.00217
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00163
AC:
248
AN:
152262
Hom.:
3
Cov.:
33
AF XY:
0.00199
AC XY:
148
AN XY:
74432
show subpopulations
Gnomad4 AFR
AF:
0.0000963
Gnomad4 AMR
AF:
0.00151
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.0347
Gnomad4 SAS
AF:
0.00311
Gnomad4 FIN
AF:
0.00141
Gnomad4 NFE
AF:
0.000118
Gnomad4 OTH
AF:
0.00142
Alfa
AF:
0.000300
Hom.:
1
Bravo
AF:
0.00159
Asia WGS
AF:
0.0120
AC:
41
AN:
3478
EpiCase
AF:
0.0000545
EpiControl
AF:
0.000237

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 submitterclinical testingInvitaeNov 18, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.73
Cadd
Benign
0.98
Dann
Benign
0.40

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs117853536; hg19: chr15-67500946; COSMIC: COSV56017931; API