chr3-193418687-G-A

Position:

• chr3-193418687-G-A

Variant summary

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

The NM_032279.4(ATP13A4):​c.2843-3937C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 149,464 control chromosomes in the GnomAD database, including 4,533 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 0.17 (4533 hom., cov: 30)
• Consequence: ATP13A4 NM_032279.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.94

Genes affected

ATP13A4 (HGNC:25422): (ATPase 13A4) Predicted to enable ATPase-coupled cation transmembrane transporter activity. Predicted to be involved in cellular calcium ion homeostasis. Predicted to be located in endoplasmic reticulum membrane and endosome membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP13A4	NM_032279.4	c.2843-3937C>T		intron_variant		ENST00000342695.9
ATP13A4	XM_047449063.1	c.2972-3937C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP13A4	ENST00000342695.9	c.2843-3937C>T		intron_variant		1	NM_032279.4	P1

Frequencies

GnomAD3 genomes AF: 0.173 AC: 25861 AN: 149352 Hom.: 4522 Cov.: 30

Gnomad AFR AF: 0.377

Gnomad AMI AF: 0.0958

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.0805

Gnomad EAS AF: 0.265

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.0698

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0731

Gnomad OTH AF: 0.140

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

GnomAD4 genome AF: 0.173 AC: 25913 AN: 149464 Hom.: 4533 Cov.: 30 AF XY: 0.174 AC XY: 12689 AN XY: 72928

Gnomad4 AFR AF: 0.377

Gnomad4 AMR AF: 0.148

Gnomad4 ASJ AF: 0.0805

Gnomad4 EAS AF: 0.265

Gnomad4 SAS AF: 0.179

Gnomad4 FIN AF: 0.0698

Gnomad4 NFE AF: 0.0731

Gnomad4 OTH AF: 0.140

Alfa AF: 0.0915 Hom.: 1100

Asia WGS AF: 0.224 AC: 761 AN: 3396

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.6
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: rs7630292; hg19: chr3-193136476;