5-82312697-A-G

Position:

• chr5-82312697-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NR_172122.1(ATP6AP1L):​n.2355A>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 0.00000207 in 1,447,590 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ATP6AP1L NR_172122.1 non_coding_transcript_exon
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.97

Genes affected

(HGNC:):

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13334224).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP6AP1L	NR_172122.1	n.2355A>G		non_coding_transcript_exon_variant	9/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000508366.5	n.1436A>G		non_coding_transcript_exon_variant	2/8	2
ATP6AP1L	ENST00000643922.1	n.570A>G		non_coding_transcript_exon_variant	6/7
	ENST00000380167.8	n.1543A>G		non_coding_transcript_exon_variant	9/10	2
	ENST00000514672.1	n.259A>G		non_coding_transcript_exon_variant	2/3	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000207 AC: 3 AN: 1447590 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 719778

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: 0.00000271

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 17, 2024

The c.218A>G (p.Q73R) alteration is located in exon 3 (coding exon 3) of the ATP6AP1L gene. This alteration results from a A to G substitution at nucleotide position 218, causing the glutamine (Q) at amino acid position 73 to be replaced by an arginine (R). 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	0.088
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	7.2
DANN	Benign	0.87
DEOGEN2	Benign	0.014	T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.47
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	1.6	L
MutationTaster	Benign	0.79	D;D
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.054
Sift	Benign	0.22	T
Sift4G	Benign	0.083	T
Polyphen		0.023	B
Vest4		0.044
MutPred		0.34		Gain of MoRF binding (P = 0.0416);
MVP		0.014
ClinPred		0.40	T
GERP RS		3.2
Varity_R		0.13
gMVP		0.38

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-81608516;