ATP6AP2 p.Ser105Arg

Variant names:

• chrX-40597261-A-C
• NM_005765.3:c.313A>C
• ATP6AP2 p.Ser105Arg

Your query was ambiguous. Multiple possible variants found:

• chrX-40597261-A-C
• chrX-40597263-T-A
• chrX-40597263-T-G
• chrX-40597261-AGT-CGC
• chrX-40597261-AGT-CGA
• chrX-40597261-AGT-CGG

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_005765.3(ATP6AP2):​c.313A>C​(p.Ser105Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 24)
• Consequence: ATP6AP2 NM_005765.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.83
• Publications: 0 publications found

Genes affected

ATP6AP2 (HGNC:18305): (ATPase H+ transporting accessory protein 2) This gene encodes a protein that is associated with adenosine triphosphatases (ATPases). Proton-translocating ATPases have fundamental roles in energy conservation, secondary active transport, acidification of intracellular compartments, and cellular pH homeostasis. There are three classes of ATPases- F, P, and V. The vacuolar (V-type) ATPases have a transmembrane proton-conducting sector and an extramembrane catalytic sector. The encoded protein has been found associated with the transmembrane sector of the V-type ATPases. [provided by RefSeq, Jul 2008]

ATP6AP2 Gene-Disease associations (from GenCC):

• ATP6AP2-related disorder

  Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
• congenital disorder of glycosylation, type IIr

  Inheritance: XL Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• syndromic X-linked intellectual disability Hedera type

  Inheritance: XL Classification: STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet, G2P, Genomics England PanelApp
• X-linked parkinsonism-spasticity syndrome

  Inheritance: XL, Unknown Classification: MODERATE, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), Genomics England PanelApp

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005765.3. 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
	ATP6AP2	NM_005765.3	MANE Select	c.313A>C	p.Ser105Arg	missense	Exon 4 of 9	NP_005756.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP6AP2	ENST00000636580.2	TSL:1 MANE Select	c.313A>C	p.Ser105Arg	missense	Exon 4 of 9	ENSP00000490083.1	O75787-1
	ATP6AP2	ENST00000636639.1	TSL:1	n.313A>C		non_coding_transcript_exon	Exon 4 of 10	ENSP00000490382.1	A0A1B0GV60
	ATP6AP2	ENST00000901377.1		c.313A>C	p.Ser105Arg	missense	Exon 4 of 9	ENSP00000571436.1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.83
BayesDel_addAF	Benign	-0.094	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.10	T
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D
M_CAP	Uncertain	0.19	D
MetaRNN	Uncertain	0.46	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L
PhyloP100		8.8
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.28
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0030	D
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.80
gMVP		0.66
Mutation Taster		=46/54	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chrX-40456513;