X-154428764-G-T

Variant names:

• chrX-154428764-G-T
• rs1326616907
• NM_001183.6:c.72G>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP7 BS2

The NM_001183.6(ATP6AP1):​c.72G>T​(p.Pro24Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000588 in 1,020,921 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes 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. P24P) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 25)
  • Exomes 𝑓: 0.0000059 (0 hom. 3 hem.)
• Consequence: ATP6AP1 NM_001183.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.265
• 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP7: Synonymous conserved (PhyloP=0.265 with no splicing effect.
• BS2: High Hemizygotes in GnomAdExome4 at 3 XL,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP6AP1	NM_001183.6	c.72G>T	p.Pro24Pro	synonymous_variant	Exon 1 of 10	ENST00000369762.7	NP_001174.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP6AP1	ENST00000369762.7	c.72G>T	p.Pro24Pro	synonymous_variant	Exon 1 of 10	1	NM_001183.6	ENSP00000358777.2

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome AF: 0.00000588 AC: 6 AN: 1020921 Hom.: 0 Cov.: 31 AF XY: 0.00000910 AC XY: 3 AN XY: 329781

African (AFR) AF: 0.00 AC: 0 AN: 21396

American (AMR) AF: 0.00 AC: 0 AN: 23698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17421

East Asian (EAS) AF: 0.00 AC: 0 AN: 24298

South Asian (SAS) AF: 0.00 AC: 0 AN: 47450

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29517

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3823

European-Non Finnish (NFE) AF: 0.00000741 AC: 6 AN: 810186

Other (OTH) AF: 0.00 AC: 0 AN: 43132

GnomAD4 genome Cov.: 25

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	8.1
DANN	Benign	0.84
PhyloP100		0.27
PromoterAI		0.065	Neutral

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: rs1326616907; hg19: chrX-153657110;