5-82318085-G-T

Variant names:

• chr5-82318085-G-T
• rs200466976
• ENST00000380167.8:n.1785G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000380167.8(ENSG00000293465):​n.1785G>T variant causes a non coding transcript exon change. The variant allele was found at a frequency of 0.00000137 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ENSG00000293465 ENST00000380167.8 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.60
• Publications: 0 publications found

Genes affected

ENSG00000293465 (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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.41525066).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000380167.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP6AP1L	NR_169868.1		n.1605G>T		non_coding_transcript_exon	Exon 7 of 7
	ATP6AP1L	NR_169870.1		n.2430G>T		non_coding_transcript_exon	Exon 12 of 12
	ATP6AP1L	NR_172106.1		n.2024G>T		non_coding_transcript_exon	Exon 10 of 10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000293465	ENST00000380167.8	TSL:2	n.1785G>T		non_coding_transcript_exon	Exon 10 of 10
	ENSG00000293465	ENST00000514672.1	TSL:2	n.501G>T		non_coding_transcript_exon	Exon 3 of 3
	ATP6AP1L	ENST00000643922.1		n.812G>T		non_coding_transcript_exon	Exon 7 of 7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461886 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727240

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1112004

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.084	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.048	T
Eigen	Uncertain	0.31
Eigen_PC	Benign	0.22
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.42	T
MetaSVM	Benign	-0.66	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		4.6
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.25
Sift	Uncertain	0.022	D
Sift4G	Uncertain	0.039	D
Polyphen		0.99	D
Vest4		0.45
MutPred		0.44		Gain of catalytic residue at L150 (P = 0.122)
MVP		0.26
ClinPred		0.93	D
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.28
gMVP		0.25

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

Other links and lift over

dbSNP: rs200466976; hg19: chr5-81613904;