Genetic Variant ATP6AP1L:n.1929G>C (chr5-82318229-G-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000380167.8(ATP6AP1L):n.1929G>C variant causes a non coding transcript exon change. The variant allele was found at a frequency of 0.0000143 in 1,613,674 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

ATP6AP1L
ENST00000380167.8 non_coding_transcript_exon

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.11

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.29907066).

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
ATP6AP1L	NR_169868.1 link	n.1749G>C	non_coding_transcript_exon_variant	Exon 7 of 7
ATP6AP1L	NR_169870.1 link	n.2574G>C	non_coding_transcript_exon_variant	Exon 12 of 12
ATP6AP1L	NR_172106.1 link	n.2168G>C	non_coding_transcript_exon_variant	Exon 10 of 10

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
ATP6AP1L	ENST00000380167.8 link	n.1929G>C	non_coding_transcript_exon_variant	Exon 10 of 10	2
ATP6AP1L	ENST00000514672.1 link	n.645G>C	non_coding_transcript_exon_variant	Exon 3 of 3	2
ATP6AP1L	ENST00000643922.1 link	n.956G>C	non_coding_transcript_exon_variant	Exon 7 of 7
ATP6AP1L	ENST00000508366.5 link	n.1590+5378G>C	intron_variant	Intron 2 of 7	2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000199

AC:

AN:

251350

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135838

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000440

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000151

AC:

AN:

1461512

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

727066

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.0000171

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152162

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000450

Hom.:

Bravo

AF:

0.0000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 27, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.604G>C (p.E202Q) alteration is located in exon 4 (coding exon 4) of the ATP6AP1L gene. This alteration results from a G to C substitution at nucleotide position 604, causing the glutamic acid (E) at amino acid position 202 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.086

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.82

M_CAP

Benign

0.0079

MetaRNN

Benign

0.30

MetaSVM

Benign

-0.35

MutationAssessor

Uncertain

2.4

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.3

REVEL

Uncertain

0.29

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.012

Polyphen

0.76

Vest4

0.52

MutPred

0.14

Gain of methylation at K201 (P = 0.1505);

MVP

0.23

ClinPred

0.83

GERP RS

5.5

Varity_R

0.22

gMVP

0.32

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