GeneBe

X-154428787-TGGCGGCGGCGGC-TGGCGGCGGCGGCGGCGGCGGCGGCGGC

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP3

The NM_001183.6(ATP6AP1):​c.102_116dupGGCGGCGGCGGCGGC​(p.Ala35_Ala39dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000178 in 1,124,708 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 0 hem., cov: 21)
Exomes 𝑓: 9.9e-7 ( 0 hom. 0 hem. )

Consequence

ATP6AP1
NM_001183.6 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.146

Publications

3 publications found
Variant links:
Genes affected
ATP6AP1 (HGNC:868): (ATPase H+ transporting accessory protein 1) This gene encodes a component of a multisubunit enzyme that mediates acidification of eukaryotic intracellular organelles. Vacuolar ATPase (V-ATPase) is comprised of a cytosolic V1 (site of the ATP catalytic site) and a transmembrane V0 domain. V-ATPase dependent organelle acidification is necessary for such intracellular processes as protein sorting, zymogen activation, and receptor-mediated endocytosis. The encoded protein of this gene may assist in the V-ATPase-mediated acidification of neuroendocrine secretory granules. This protein may also play a role in early development. [provided by RefSeq, Aug 2013]
ATP6AP1-DT (HGNC:25138): (ATP6AP1 divergent transcript)

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_001183.6, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP3
Nonframeshift variant in repetitive region in NM_001183.6

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001183.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
ATP6AP1
NM_001183.6
MANE Select
c.102_116dupGGCGGCGGCGGCGGCp.Ala35_Ala39dup
disruptive_inframe_insertion
Exon 1 of 10NP_001174.2

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
ATP6AP1
ENST00000369762.7
TSL:1 MANE Select
c.102_116dupGGCGGCGGCGGCGGCp.Ala35_Ala39dup
disruptive_inframe_insertion
Exon 1 of 10ENSP00000358777.2Q15904
ATP6AP1
ENST00000945275.1
c.102_116dupGGCGGCGGCGGCGGCp.Ala35_Ala39dup
disruptive_inframe_insertion
Exon 1 of 11ENSP00000615334.1
ATP6AP1
ENST00000862438.1
c.102_116dupGGCGGCGGCGGCGGCp.Ala35_Ala39dup
disruptive_inframe_insertion
Exon 1 of 10ENSP00000532497.1

Frequencies

GnomAD3 genomes
AF:
0.00000892
AC:
1
AN:
112151
Hom.:
0
Cov.:
21
show subpopulations
Gnomad AFR
AF:
0.0000327
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
9.88e-7
AC:
1
AN:
1012557
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
325981
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
20805
American (AMR)
AF:
0.00
AC:
0
AN:
22655
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
16951
East Asian (EAS)
AF:
0.00
AC:
0
AN:
24117
South Asian (SAS)
AF:
0.00
AC:
0
AN:
46153
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
28515
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
3624
European-Non Finnish (NFE)
AF:
0.00000124
AC:
1
AN:
806973
Other (OTH)
AF:
0.00
AC:
0
AN:
42764
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.375
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
AF:
0.00000892
AC:
1
AN:
112151
Hom.:
0
Cov.:
21
AF XY:
0.00
AC XY:
0
AN XY:
34497
show subpopulations
African (AFR)
AF:
0.0000327
AC:
1
AN:
30584
American (AMR)
AF:
0.00
AC:
0
AN:
10784
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
2641
East Asian (EAS)
AF:
0.00
AC:
0
AN:
3556
South Asian (SAS)
AF:
0.00
AC:
0
AN:
2821
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
6209
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
235
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
53124
Other (OTH)
AF:
0.00
AC:
0
AN:
1515
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
0.00
Hom.:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
PhyloP100
0.15

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

Other links and lift over

dbSNP: rs781797236;
hg19: chrX-153657133;
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