Menu
GeneBe

X-40581031-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_005765.3(ATP6AP2):c.-35G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00196 in 1,162,744 control chromosomes in the GnomAD database, including 27 homozygotes. There are 622 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0099 ( 18 hom., 325 hem., cov: 24)
Exomes 𝑓: 0.0011 ( 9 hom. 297 hem. )

Consequence

ATP6AP2
NM_005765.3 5_prime_UTR

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.00600
Variant links:
Genes affected
ATP6AP2 (HGNC:18305): (ATPase H+ transporting accessory protein 2) This gene encodes a protein that is associated with adenosine triphosphatases (ATPases). Proton-translocating ATPases have fundamental roles in energy conservation, secondary active transport, acidification of intracellular compartments, and cellular pH homeostasis. There are three classes of ATPases- F, P, and V. The vacuolar (V-type) ATPases have a transmembrane proton-conducting sector and an extramembrane catalytic sector. The encoded protein has been found associated with the transmembrane sector of the V-type ATPases. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 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=-0.49).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant X-40581031-G-C is Benign according to our data. Variant chrX-40581031-G-C is described in ClinVar as [Benign]. Clinvar id is 136464.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00994 (1126/113284) while in subpopulation AFR AF= 0.0342 (1072/31308). AF 95% confidence interval is 0.0325. There are 18 homozygotes in gnomad4. There are 325 alleles in male gnomad4 subpopulation. Median coverage is 24. 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 Homozygotes in GnomAd at 18 XL gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ATP6AP2NM_005765.3 linkuse as main transcriptc.-35G>C 5_prime_UTR_variant 1/9 ENST00000636580.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ATP6AP2ENST00000636580.2 linkuse as main transcriptc.-35G>C 5_prime_UTR_variant 1/91 NM_005765.3 P3O75787-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00994
AC:
1125
AN:
113235
Hom.:
18
Cov.:
24
AF XY:
0.00915
AC XY:
324
AN XY:
35401
show subpopulations
Gnomad AFR
AF:
0.0343
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00331
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:
0.0000938
Gnomad OTH
AF:
0.00851
GnomAD3 exomes
AF:
0.00237
AC:
245
AN:
103268
Hom.:
1
AF XY:
0.00149
AC XY:
55
AN XY:
36924
show subpopulations
Gnomad AFR exome
AF:
0.0386
Gnomad AMR exome
AF:
0.00130
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000355
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000269
Gnomad OTH exome
AF:
0.000647
GnomAD4 exome
AF:
0.00110
AC:
1157
AN:
1049460
Hom.:
9
Cov.:
30
AF XY:
0.000867
AC XY:
297
AN XY:
342370
show subpopulations
Gnomad4 AFR exome
AF:
0.0393
Gnomad4 AMR exome
AF:
0.00147
Gnomad4 ASJ exome
AF:
0.0000539
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000141
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000183
Gnomad4 OTH exome
AF:
0.00258
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00994
AC:
1126
AN:
113284
Hom.:
18
Cov.:
24
AF XY:
0.00917
AC XY:
325
AN XY:
35460
show subpopulations
Gnomad4 AFR
AF:
0.0342
Gnomad4 AMR
AF:
0.00330
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000938
Gnomad4 OTH
AF:
0.00840
Alfa
AF:
0.00543
Hom.:
22
Bravo
AF:
0.0121

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxFeb 28, 2013This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.49
Cadd
Benign
7.7
Dann
Benign
0.84
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

Publications

LitVar

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

Other links and lift over

dbSNP: rs111632930; hg19: chrX-40440283; API