Variant X-40580946-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000636639.1(ATP6AP2):c.-120G>C variant causes a 5 prime UTR, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.016 in 897,190 control chromosomes in the GnomAD database, including 100 homozygotes. There are 4,188 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 17 hom., 646 hem., cov: 25)

Exomes 𝑓: 0.016 ( 83 hom. 3542 hem. )

Consequence

ATP6AP2
ENST00000636639.1 5_prime_UTR, NMD_transcript

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.367

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]

ATP6AP2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant X-40580946-G-C is Benign according to our data. Variant chrX-40580946-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 670923.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0188 (2127/113291) while in subpopulation AFR AF= 0.0251 (785/31294). AF 95% confidence interval is 0.0236. There are 17 homozygotes in gnomad4. There are 646 alleles in male gnomad4 subpopulation. Median coverage is 25. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 17 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP6AP2	NM_005765.3 linkuse as main transcript			upstream_gene_variant		ENST00000636580.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP6AP2	ENST00000636580.2 linkuse as main transcript			upstream_gene_variant		1	NM_005765.3	P3	O75787-1

Frequencies

GnomAD3 genomes

AF:

0.0188

AC:

2125

AN:

113241

Hom.:

Cov.:

AF XY:

0.0182

AC XY:

645

AN XY:

35391

show subpopulations

Gnomad AFR

AF:

0.0251

Gnomad AMI

AF:

0.0338

Gnomad AMR

AF:

0.0120

Gnomad ASJ

AF:

0.00789

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0145

Gnomad FIN

AF:

0.0398

Gnomad MID

AF:

0.0500

Gnomad NFE

AF:

0.0155

Gnomad OTH

AF:

0.0235

GnomAD3 exomes

AF:

0.0146

AC:

1466

AN:

100409

Hom.:

AF XY:

0.0138

AC XY:

501

AN XY:

36295

show subpopulations

Gnomad AFR exome

AF:

0.0291

Gnomad AMR exome

AF:

0.00658

Gnomad ASJ exome

AF:

0.00841

Gnomad EAS exome

AF:

0.000255

Gnomad SAS exome

AF:

0.0135

Gnomad FIN exome

AF:

0.0388

Gnomad NFE exome

AF:

0.0165

Gnomad OTH exome

AF:

0.0181

GnomAD4 exome

AF:

0.0156

AC:

12205

AN:

783899

Hom.:

Cov.:

AF XY:

0.0164

AC XY:

3542

AN XY:

216343

show subpopulations

Gnomad4 AFR exome

AF:

0.0265

Gnomad4 AMR exome

AF:

0.00763

Gnomad4 ASJ exome

AF:

0.00975

Gnomad4 EAS exome

AF:

0.000117

Gnomad4 SAS exome

AF:

0.0133

Gnomad4 FIN exome

AF:

0.0371

Gnomad4 NFE exome

AF:

0.0153

Gnomad4 OTH exome

AF:

0.0170

GnomAD4 genome

AF:

0.0188

AC:

2127

AN:

113291

Hom.:

Cov.:

AF XY:

0.0182

AC XY:

646

AN XY:

35451

show subpopulations

Gnomad4 AFR

AF:

0.0251

Gnomad4 AMR

AF:

0.0120

Gnomad4 ASJ

AF:

0.00789

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0145

Gnomad4 FIN

AF:

0.0398

Gnomad4 NFE

AF:

0.0155

Gnomad4 OTH

AF:

0.0232

Alfa

AF:

0.00900

Hom.:

Bravo

AF:

0.0176

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	This 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

-0.78

CADD

Benign

4.9

DANN

Benign

0.60

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over