X-40605752-T-C

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_005765.3(ATP6AP2):ā€‹c.1050T>Cā€‹(p.Asp350Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000251 in 1,201,956 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 82 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā˜…ā˜…).

Frequency

Genomes: š‘“ 0.0013 ( 0 hom., 39 hem., cov: 23)
Exomes š‘“: 0.00014 ( 0 hom. 43 hem. )

Consequence

ATP6AP2
NM_005765.3 synonymous

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.746
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.6).
BP6
Variant X-40605752-T-C is Benign according to our data. Variant chrX-40605752-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 199113.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-40605752-T-C is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=0.746 with no splicing effect.
BS2
High Hemizygotes in GnomAd4 at 39 XL gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ATP6AP2NM_005765.3 linkuse as main transcriptc.1050T>C p.Asp350Asp synonymous_variant 9/9 ENST00000636580.2 NP_005756.2 O75787-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ATP6AP2ENST00000636580.2 linkuse as main transcriptc.1050T>C p.Asp350Asp synonymous_variant 9/91 NM_005765.3 ENSP00000490083.1 O75787-1

Frequencies

GnomAD3 genomes
AF:
0.00133
AC:
149
AN:
111961
Hom.:
0
Cov.:
23
AF XY:
0.00114
AC XY:
39
AN XY:
34123
show subpopulations
Gnomad AFR
AF:
0.00451
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000953
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
GnomAD3 exomes
AF:
0.000382
AC:
70
AN:
183039
Hom.:
0
AF XY:
0.000222
AC XY:
15
AN XY:
67571
show subpopulations
Gnomad AFR exome
AF:
0.00464
Gnomad AMR exome
AF:
0.000292
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000222
GnomAD4 exome
AF:
0.000140
AC:
153
AN:
1089943
Hom.:
0
Cov.:
29
AF XY:
0.000121
AC XY:
43
AN XY:
356295
show subpopulations
Gnomad4 AFR exome
AF:
0.00465
Gnomad4 AMR exome
AF:
0.000284
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000479
Gnomad4 OTH exome
AF:
0.000349
GnomAD4 genome
AF:
0.00133
AC:
149
AN:
112013
Hom.:
0
Cov.:
23
AF XY:
0.00114
AC XY:
39
AN XY:
34185
show subpopulations
Gnomad4 AFR
AF:
0.00450
Gnomad4 AMR
AF:
0.000952
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000569
Hom.:
0
Bravo
AF:
0.00174

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:2
Benign, criteria provided, single submitterclinical testingEurofins Ntd Llc (ga)Jan 06, 2015- -
Benign, criteria provided, single submitterclinical testingGeneDxSep 17, 2014This 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. -
Syndromic X-linked intellectual disability Hedera type Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 30, 2024- -
Syndromic X-linked intellectual disability Hedera type;C3806722:X-linked parkinsonism-spasticity syndrome;C5393313:Congenital disorder of glycosylation, type IIr Benign:1
Likely benign, criteria provided, single submitterclinical testingFulgent Genetics, Fulgent GeneticsJan 24, 2022- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.60
CADD
Benign
5.5
DANN
Benign
0.42

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: rs79790275; hg19: chrX-40465004; API