Genetic Variant ATP6AP1L:n.1703A>G (chr5-82318003-A-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000380167.8(ATP6AP1L):n.1703A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00076 in 1,614,116 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00043 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00079 ( 22 hom. )

Consequence

ATP6AP1L
ENST00000380167.8 non_coding_transcript_exon

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.21

Variant links:

Genes affected

ATP6AP1L (HGNC:28091): (ATPase H+ transporting accessory protein 1 like (pseudogene)) Predicted to be involved in regulation of cellular pH. Predicted to be integral component of membrane. Predicted to be part of plasma membrane proton-transporting V-type ATPase complex. [provided by Alliance of Genome Resources, Apr 2022]

ATP6AP1L links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 5-82318003-A-G is Benign according to our data. Variant chr5-82318003-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2655575.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 22 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
ATP6AP1L	NR_169868.1 link	n.1523A>G	non_coding_transcript_exon_variant	Exon 7 of 7
ATP6AP1L	NR_169870.1 link	n.2348A>G	non_coding_transcript_exon_variant	Exon 12 of 12
ATP6AP1L	NR_172106.1 link	n.1942A>G	non_coding_transcript_exon_variant	Exon 10 of 10

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
ATP6AP1L	ENST00000380167.8 link	n.1703A>G	non_coding_transcript_exon_variant	Exon 10 of 10	2
ATP6AP1L	ENST00000514672.1 link	n.419A>G	non_coding_transcript_exon_variant	Exon 3 of 3	2
ATP6AP1L	ENST00000643922.1 link	n.730A>G	non_coding_transcript_exon_variant	Exon 7 of 7
ATP6AP1L	ENST00000508366.5 link	n.1590+5152A>G	intron_variant	Intron 2 of 7	2

Frequencies

GnomAD3 genomes

AF:

0.000427

AC:

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0108

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00138

AC:

345

AN:

250242

Hom.:

AF XY:

0.00188

AC XY:

254

AN XY:

135340

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00974

Gnomad FIN exome

AF:

0.0000463

Gnomad NFE exome

AF:

0.000293

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.000794

AC:

1161

AN:

1461806

Hom.:

Cov.:

AF XY:

0.00110

AC XY:

802

AN XY:

727200

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000894

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0101

Gnomad4 FIN exome

AF:

0.0000936

Gnomad4 NFE exome

AF:

0.000178

Gnomad4 OTH exome

AF:

0.000911

GnomAD4 genome

AF:

0.000427

AC:

AN:

152310

Hom.:

Cov.:

AF XY:

0.000591

AC XY:

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0108

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000196

Hom.:

Bravo

AF:

0.000125

Asia WGS

AF:

0.00433

AC:

AN:

3478

EpiCase

AF:

0.000382

EpiControl

AF:

0.000356

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Nov 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ATP6AP1L: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.49

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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