ENST00000380167.8:n.1917G>C

Variant names:

• chr5-82318217-G-C
• ENST00000380167.8:n.1917G>C

Variant summary

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

The ENST00000380167.8(ATP6AP1L):​n.1917G>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: ATP6AP1L ENST00000380167.8 non_coding_transcript_exon
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.01

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13227388).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP6AP1L	NR_169868.1	n.1737G>C		non_coding_transcript_exon_variant	Exon 7 of 7
ATP6AP1L	NR_169870.1	n.2562G>C		non_coding_transcript_exon_variant	Exon 12 of 12
ATP6AP1L	NR_172106.1	n.2156G>C		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.1917G>C		non_coding_transcript_exon_variant	Exon 10 of 10	2
ATP6AP1L	ENST00000514672.1	n.633G>C		non_coding_transcript_exon_variant	Exon 3 of 3	2
ATP6AP1L	ENST00000643922.1	n.944G>C		non_coding_transcript_exon_variant	Exon 7 of 7
ATP6AP1L	ENST00000508366.5	n.1590+5366G>C		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 07, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.592G>C (p.A198P) 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 592, causing the alanine (A) at amino acid position 198 to be replaced by a proline (P). 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	0.12
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	2.5
DANN	Uncertain	1.0
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.9	L
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.045
Sift	Uncertain	0.020	D
Sift4G	Uncertain	0.038	D
Polyphen		0.091	B
Vest4		0.48
MutPred		0.15		Gain of glycosylation at A198 (P = 0.0338);
MVP		0.048
ClinPred		0.47	T
GERP RS		1.7
Varity_R		0.21
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-81614036;