rs782480523

Variant names:

• chrX-154428710-G-A
• rs782480523
• NM_001183.6:c.18G>A

Your query was ambiguous. Multiple possible variants found:

• chrX-154428710-G-A
• chrX-154428710-G-T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001183.6(ATP6AP1):​c.18G>A​(p.Ala6Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000193 in 1,035,686 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A6A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 25)
  • Exomes 𝑓: 0.0000019 (0 hom. 0 hem.)
• Consequence: ATP6AP1 NM_001183.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0280
• Publications: 2 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BP7: Synonymous conserved (PhyloP=-0.028 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP6AP1	NM_001183.6	c.18G>A	p.Ala6Ala	synonymous_variant	Exon 1 of 10	ENST00000369762.7	NP_001174.2
ATP6AP1-DT	NR_103768.1	n.-231C>T		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP6AP1	ENST00000369762.7	c.18G>A	p.Ala6Ala	synonymous_variant	Exon 1 of 10	1	NM_001183.6	ENSP00000358777.2

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD2 exomes AF: 0.0000234 AC: 2 AN: 85587 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000555

Gnomad ASJ exome AF: 0.000182

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000193 AC: 2 AN: 1035686 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 336470

African (AFR) AF: 0.00 AC: 0 AN: 22667

American (AMR) AF: 0.0000368 AC: 1 AN: 27166

Ashkenazi Jewish (ASJ) AF: 0.0000549 AC: 1 AN: 18212

East Asian (EAS) AF: 0.00 AC: 0 AN: 25371

South Asian (SAS) AF: 0.00 AC: 0 AN: 49275

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30019

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3987

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 815143

Other (OTH) AF: 0.00 AC: 0 AN: 43846

GnomAD4 genome Cov.: 25

Alfa AF: 0.000338 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	6.6
DANN	Benign	0.92
PhyloP100		-0.028
PromoterAI		-0.75	Under-expression

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: rs782480523; hg19: chrX-153657056;