chrX-154428727-T-G

Variant names:

• chrX-154428727-T-G
• rs2068677249
• NM_001183.6:c.35T>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001183.6(ATP6AP1):​c.35T>G​(p.Met12Arg) variant causes a missense 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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 25)
• Consequence: ATP6AP1 NM_001183.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0200
• Publications: 0 publications found

Genes affected

ATP6AP1 (HGNC:868): (ATPase H+ transporting accessory protein 1) This gene encodes a component of a multisubunit enzyme that mediates acidification of eukaryotic intracellular organelles. Vacuolar ATPase (V-ATPase) is comprised of a cytosolic V1 (site of the ATP catalytic site) and a transmembrane V0 domain. V-ATPase dependent organelle acidification is necessary for such intracellular processes as protein sorting, zymogen activation, and receptor-mediated endocytosis. The encoded protein of this gene may assist in the V-ATPase-mediated acidification of neuroendocrine secretory granules. This protein may also play a role in early development. [provided by RefSeq, Aug 2013]

ATP6AP1-DT (HGNC:25138): (ATP6AP1 divergent transcript)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07123238).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001183.6. 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
	ATP6AP1	NM_001183.6	MANE Select	c.35T>G	p.Met12Arg	missense	Exon 1 of 10	NP_001174.2
	ATP6AP1-DT	NR_103768.1		n.-248A>C		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP6AP1	ENST00000369762.7	TSL:1 MANE Select	c.35T>G	p.Met12Arg	missense	Exon 1 of 10	ENSP00000358777.2	Q15904
	ATP6AP1	ENST00000945275.1		c.35T>G	p.Met12Arg	missense	Exon 1 of 11	ENSP00000615334.1
	ATP6AP1	ENST00000862438.1		c.35T>G	p.Met12Arg	missense	Exon 1 of 10	ENSP00000532497.1

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 25

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	3.1
DANN	Benign	0.58
DEOGEN2	Benign	0.029	T
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.0089	T
MetaRNN	Benign	0.071	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.34	N
PhyloP100		-0.020
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.040	N
REVEL	Benign	0.021
Sift	Benign	0.032	D
Sift4G	Benign	0.21	T
Polyphen		0.0030	B
Vest4		0.25
MutPred		0.37		Gain of solvent accessibility (P = 8e-04)
MVP		0.12
MPC		0.40
ClinPred		0.042	T
GERP RS		0.24
PromoterAI		-0.041	Neutral
Varity_R		0.28
gMVP		0.37
Mutation Taster		=97/3	polymorphism

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: rs2068677249; hg19: chrX-153657073;