3-193325847-C-A

Position:

• chr3-193325847-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198505.4(ATP13A5):​c.1524-833G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.515 in 151,990 control chromosomes in the GnomAD database, including 22,473 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.51 (22473 hom., cov: 32)
• Consequence: ATP13A5 NM_198505.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.530

Genes affected

ATP13A5 (HGNC:31789): (ATPase 13A5) This gene encodes a member of the P5 subfamily of P-type transport ATPases. P-type ATPases form a large superfamily of cation and lipid pumps that transport inorganic cations and other substrates across cell membranes. P5 ATPases are localized to membranes of the endoplasmic reticulum (ER) and serve many important functions including transport of cargo proteins to the Golgi, glycosylation and cell wall biosynthesis, control of protein insertion orientation, 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) degradation, and sensitivity to unfolded protein response (UPR) activators. The encoded protein is organized into three cytoplasmic domains (A, P, and N) and two membrane-embedded domains (T and S). The N-domain binds ATP and serves as a built-in protein kinase, which phosphorylates the P-domain. The A-domain is an intrinsic protein phosphatase, which dephosphorylates the P-domain once during each catalytic cycle. [provided by RefSeq, Jul 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.64 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP13A5	NM_198505.4	c.1524-833G>T		intron_variant		ENST00000342358.9	NP_940907.2
ATP13A5	XM_011512770.3	c.1524-833G>T		intron_variant			XP_011511072.1
ATP13A5	XM_047448075.1	c.270-833G>T		intron_variant			XP_047304031.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP13A5	ENST00000342358.9	c.1524-833G>T		intron_variant		1	NM_198505.4	ENSP00000341942.4

Frequencies

GnomAD3 genomes AF: 0.515 AC: 78212 AN: 151872 Hom.: 22469 Cov.: 32

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.725

Gnomad AMR AF: 0.559

Gnomad ASJ AF: 0.552

Gnomad EAS AF: 0.642

Gnomad SAS AF: 0.540

Gnomad FIN AF: 0.563

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.645

Gnomad OTH AF: 0.530

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.515 AC: 78230 AN: 151990 Hom.: 22473 Cov.: 32 AF XY: 0.512 AC XY: 38047 AN XY: 74268

Gnomad4 AFR AF: 0.244

Gnomad4 AMR AF: 0.559

Gnomad4 ASJ AF: 0.552

Gnomad4 EAS AF: 0.641

Gnomad4 SAS AF: 0.541

Gnomad4 FIN AF: 0.563

Gnomad4 NFE AF: 0.645

Gnomad4 OTH AF: 0.532

Alfa AF: 0.589 Hom.: 12994

Bravo AF: 0.506

Asia WGS AF: 0.570 AC: 1983 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.1
DANN	Benign	0.41

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

Publications

LitVar

Other links and lift over

dbSNP: rs12493236; hg19: chr3-193043636;