rs1363133638

Variant names:

• chrX-154428701-G-C
• rs1363133638
• NM_001183.6:c.9G>C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_001183.6(ATP6AP1):​c.9G>C​(p.Ala3Ala) variant causes a synonymous change. The variant allele was found at a frequency of 0.0000226 in 1,149,575 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 8 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. A3A) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0000088 (0 hom., 0 hem., cov: 25)
  • Exomes 𝑓: 0.000024 (0 hom. 8 hem.)
• Consequence: ATP6AP1 NM_001183.6 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.71
• 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BP6: Variant X-154428701-G-C is Benign according to our data. Variant chrX-154428701-G-C is described in ClinVar as Likely_benign. ClinVar VariationId is 1900748.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAdExome4 at 8 XL,AR gene

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.9G>C	p.Ala3Ala	synonymous	Exon 1 of 10	NP_001174.2
	ATP6AP1-DT	NR_103768.1		n.-222C>G		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.9G>C	p.Ala3Ala	synonymous	Exon 1 of 10	ENSP00000358777.2	Q15904
	ATP6AP1	ENST00000945275.1		c.9G>C	p.Ala3Ala	synonymous	Exon 1 of 11	ENSP00000615334.1
	ATP6AP1	ENST00000862438.1		c.9G>C	p.Ala3Ala	synonymous	Exon 1 of 10	ENSP00000532497.1

Frequencies

GnomAD3 genomes AF: 0.00000879 AC: 1 AN: 113734 Hom.: 0 Cov.: 25

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000187

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000232 AC: 2 AN: 86079 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000628

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000241 AC: 25 AN: 1035841 Hom.: 0 Cov.: 30 AF XY: 0.0000238 AC XY: 8 AN XY: 336645

African (AFR) AF: 0.00 AC: 0 AN: 22672

American (AMR) AF: 0.0000368 AC: 1 AN: 27204

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18213

East Asian (EAS) AF: 0.00 AC: 0 AN: 25405

South Asian (SAS) AF: 0.00 AC: 0 AN: 49291

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29970

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3995

European-Non Finnish (NFE) AF: 0.0000270 AC: 22 AN: 815228

Other (OTH) AF: 0.0000456 AC: 2 AN: 43863

GnomAD4 genome AF: 0.00000879 AC: 1 AN: 113734 Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0 AN XY: 35860

African (AFR) AF: 0.00 AC: 0 AN: 31383

American (AMR) AF: 0.00 AC: 0 AN: 10884

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2665

East Asian (EAS) AF: 0.00 AC: 0 AN: 3611

South Asian (SAS) AF: 0.00 AC: 0 AN: 2882

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 237

European-Non Finnish (NFE) AF: 0.0000187 AC: 1 AN: 53446

Other (OTH) AF: 0.00 AC: 0 AN: 1542

Alfa AF: 0.0000436 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	14
DANN	Benign	0.84
PhyloP100		5.7
PromoterAI		-0.23	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6

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: rs1363133638; hg19: chrX-153657047;