ENST00000380167.8:n.1530A>C

Variant names:

• chr5-82312684-A-C
• rs147393251
• ENST00000380167.8:n.1530A>C

Variant summary

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

The ENST00000380167.8(ATP6AP1L):​n.1530A>C variant causes a non coding transcript exon change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,449,872 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ATP6AP1L ENST00000380167.8 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.25

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP6AP1L	NR_169870.1	n.2175A>C		non_coding_transcript_exon_variant	Exon 11 of 12
ATP6AP1L	NR_172106.1	n.1769A>C		non_coding_transcript_exon_variant	Exon 9 of 10
ATP6AP1L	NR_172107.1	n.2269A>C		non_coding_transcript_exon_variant	Exon 10 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP6AP1L	ENST00000380167.8	n.1530A>C		non_coding_transcript_exon_variant	Exon 9 of 10	2
ATP6AP1L	ENST00000508366.5	n.1423A>C		non_coding_transcript_exon_variant	Exon 2 of 8	2
ATP6AP1L	ENST00000514672.1	n.246A>C		non_coding_transcript_exon_variant	Exon 2 of 3	2
ATP6AP1L	ENST00000643922.1	n.557A>C		non_coding_transcript_exon_variant	Exon 6 of 7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000842 AC: 2 AN: 237624 Hom.: 0 AF XY: 0.00000776 AC XY: 1 AN XY: 128864

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: 0.0000703

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1449872 Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1 AN XY: 721024

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: 0.0000238

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.086	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	14
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	T
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.026	D
MetaRNN	Uncertain	0.74	D
MetaSVM	Uncertain	0.053	D
MutationAssessor	Uncertain	2.7	M
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-3.6	D
REVEL	Uncertain	0.52
Sift	Benign	0.032	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.67
MutPred		0.47		Gain of catalytic residue at N70 (P = 0.0954);
MVP		0.072
ClinPred		0.89	D
GERP RS		5.7
Varity_R		0.83
gMVP		0.61

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

Other links and lift over

dbSNP: rs147393251; hg19: chr5-81608503;