rs12493236

Variant names:

• chr3-193325847-C-A
• rs12493236
• NM_198505.4:c.1524-833G>T

Your query was ambiguous. Multiple possible variants found:

• chr3-193325847-C-A
• chr3-193325847-C-G
• chr3-193325847-C-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198505.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP13A5	NM_198505.4	MANE Select	c.1524-833G>T		intron	N/A	NP_940907.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP13A5	ENST00000342358.9	TSL:1 MANE Select	c.1524-833G>T		intron	N/A	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

African (AFR) AF: 0.244 AC: 10113 AN: 41446

American (AMR) AF: 0.559 AC: 8548 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.552 AC: 1915 AN: 3472

East Asian (EAS) AF: 0.641 AC: 3315 AN: 5170

South Asian (SAS) AF: 0.541 AC: 2599 AN: 4802

European-Finnish (FIN) AF: 0.563 AC: 5941 AN: 10548

Middle Eastern (MID) AF: 0.538 AC: 157 AN: 292

European-Non Finnish (NFE) AF: 0.645 AC: 43861 AN: 67954

Other (OTH) AF: 0.532 AC: 1120 AN: 2104

Alfa AF: 0.585 Hom.: 18767

Bravo AF: 0.506

Asia WGS AF: 0.570 AC: 1983 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.1
DANN	Benign	0.41
PhyloP100		-0.53
Mutation Taster		=100/0	polymorphism (auto)

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: rs12493236; hg19: chr3-193043636;