5-82318014-T-C

Variant names:

• chr5-82318014-T-C
• ENST00000380167.8:n.1714T>C

Variant summary

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

The ENST00000380167.8(ATP6AP1L):​n.1714T>C variant causes a non coding transcript exon change. The variant was absent in control chromosomes in GnomAD project. 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: 5.13

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_169868.1	n.1534T>C		non_coding_transcript_exon_variant	Exon 7 of 7
ATP6AP1L	NR_169870.1	n.2359T>C		non_coding_transcript_exon_variant	Exon 12 of 12
ATP6AP1L	NR_172106.1	n.1953T>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.1714T>C		non_coding_transcript_exon_variant	Exon 10 of 10	2
ATP6AP1L	ENST00000514672.1	n.430T>C		non_coding_transcript_exon_variant	Exon 3 of 3	2
ATP6AP1L	ENST00000643922.1	n.741T>C		non_coding_transcript_exon_variant	Exon 7 of 7
ATP6AP1L	ENST00000508366.5	n.1590+5163T>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

Aug 20, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.389T>C (p.I130T) alteration is located in exon 4 (coding exon 4) of the ATP6AP1L gene. This alteration results from a T to C substitution at nucleotide position 389, causing the isoleucine (I) at amino acid position 130 to be replaced by a threonine (T). 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	0.31
BayesDel_addAF	Benign	-0.0021	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	13
DANN	Uncertain	0.99
DEOGEN2	Benign	0.10	T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.43
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.0059	T
MetaRNN	Uncertain	0.53	D
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.4	L
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.20
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.013	D
Polyphen		0.091	B
Vest4		0.57
MutPred		0.66		Loss of stability (P = 0.0088);
MVP		0.15
ClinPred		0.72	D
GERP RS		3.6
Varity_R		0.45
gMVP		0.31

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: chr5-81613833;