5-82318050-C-A

Variant names:

• chr5-82318050-C-A
• ENST00000380167.8:n.1750C>A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The ENST00000380167.8(ATP6AP1L):​n.1750C>A variant causes a non coding transcript exon change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ATP6AP1L ENST00000380167.8 non_coding_transcript_exon
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.19

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.78

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP6AP1L	NR_169868.1	n.1570C>A		non_coding_transcript_exon_variant	Exon 7 of 7
ATP6AP1L	NR_169870.1	n.2395C>A		non_coding_transcript_exon_variant	Exon 12 of 12
ATP6AP1L	NR_172106.1	n.1989C>A		non_coding_transcript_exon_variant	Exon 10 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP6AP1L	ENST00000380167.8	n.1750C>A		non_coding_transcript_exon_variant	Exon 10 of 10	2
ATP6AP1L	ENST00000514672.1	n.466C>A		non_coding_transcript_exon_variant	Exon 3 of 3	2
ATP6AP1L	ENST00000643922.1	n.777C>A		non_coding_transcript_exon_variant	Exon 7 of 7
ATP6AP1L	ENST00000508366.5	n.1590+5199C>A		intron_variant	Intron 2 of 7	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 26, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.425C>A (p.A142D) alteration is located in exon 4 (coding exon 4) of the ATP6AP1L gene. This alteration results from a C to A substitution at nucleotide position 425, causing the alanine (A) at amino acid position 142 to be replaced by an aspartic acid (D). 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	0.19
BayesDel_addAF	Uncertain	0.031	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	9.1
DANN	Uncertain	0.99
DEOGEN2	Benign	0.34	T
Eigen	Benign	0.064
Eigen_PC	Benign	-0.037
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.032	D
MetaRNN	Pathogenic	0.78	D
MetaSVM	Benign	-0.30	T
MutationAssessor	Uncertain	2.3	M
PrimateAI	Benign	0.28	T
PROVEAN	Pathogenic	-4.5	D
REVEL	Benign	0.22
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.58	P
Vest4		0.65
MutPred		0.52		Gain of relative solvent accessibility (P = 0.0082);
MVP		0.12
ClinPred		0.99	D
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.89
gMVP		0.59

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: chr5-81613869;