chr3-193489591-T-C

Position:

• chr3-193489591-T-C

Variant summary

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

The NM_032279.4(ATP13A4):​c.738+139A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.411 in 834,050 control chromosomes in the GnomAD database, including 71,508 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 0.43 (14384 hom., cov: 32)
  • Exomes 𝑓: 0.41 (57124 hom.)
• Consequence: ATP13A4 NM_032279.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00400

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.501 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP13A4	NM_032279.4	c.738+139A>G		intron_variant		ENST00000342695.9
ATP13A4	XM_017007319.2	c.867+139A>G		intron_variant
ATP13A4	XM_047449063.1	c.867+139A>G		intron_variant
ATP13A4	XR_007095757.1	n.1131+139A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP13A4	ENST00000342695.9	c.738+139A>G		intron_variant		1	NM_032279.4	P1

Frequencies

GnomAD3 genomes AF: 0.432 AC: 65647 AN: 151872 Hom.: 14368 Cov.: 32

Gnomad AFR AF: 0.506

Gnomad AMI AF: 0.377

Gnomad AMR AF: 0.479

Gnomad ASJ AF: 0.362

Gnomad EAS AF: 0.438

Gnomad SAS AF: 0.450

Gnomad FIN AF: 0.348

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.393

Gnomad OTH AF: 0.422

GnomAD4 exome AF: 0.406 AC: 277172 AN: 682060 Hom.: 57124 AF XY: 0.406 AC XY: 146869 AN XY: 361654

Gnomad4 AFR exome AF: 0.512

Gnomad4 AMR exome AF: 0.512

Gnomad4 ASJ exome AF: 0.368

Gnomad4 EAS exome AF: 0.409

Gnomad4 SAS exome AF: 0.445

Gnomad4 FIN exome AF: 0.342

Gnomad4 NFE exome AF: 0.396

Gnomad4 OTH exome AF: 0.408

GnomAD4 genome AF: 0.432 AC: 65706 AN: 151990 Hom.: 14384 Cov.: 32 AF XY: 0.431 AC XY: 32005 AN XY: 74298

Gnomad4 AFR AF: 0.506

Gnomad4 AMR AF: 0.479

Gnomad4 ASJ AF: 0.362

Gnomad4 EAS AF: 0.438

Gnomad4 SAS AF: 0.451

Gnomad4 FIN AF: 0.348

Gnomad4 NFE AF: 0.393

Gnomad4 OTH AF: 0.418

Alfa AF: 0.401 Hom.: 5806

Bravo AF: 0.445

Asia WGS AF: 0.457 AC: 1590 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.5
DANN	Benign	0.54

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: rs6444724; hg19: chr3-193207380; COSMIC: COSV55075785;