chr3-193489591-T-C

Variant names:

• chr3-193489591-T-C
• rs6444724
• NM_032279.4:c.738+139A>G

Variant summary

Our verdict is Benign. The variant received -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. Variant has been reported in ClinVar as (no stars).

• 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
• Publications: 18 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032279.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP13A4	NM_032279.4	MANE Select	c.738+139A>G		intron	N/A	NP_115655.2	Q4VNC1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP13A4	ENST00000342695.9	TSL:1 MANE Select	c.738+139A>G		intron	N/A	ENSP00000339182.4	Q4VNC1-1
	ATP13A4	ENST00000490925.5	TSL:1	n.846+139A>G		intron	N/A
	ATP13A4	ENST00000392443.7	TSL:5	c.738+139A>G		intron	N/A	ENSP00000376238.3	B7WPN9

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

African (AFR) AF: 0.512 AC: 8885 AN: 17344

American (AMR) AF: 0.512 AC: 16620 AN: 32476

Ashkenazi Jewish (ASJ) AF: 0.368 AC: 6207 AN: 16882

East Asian (EAS) AF: 0.409 AC: 14215 AN: 34724

South Asian (SAS) AF: 0.445 AC: 26261 AN: 59060

European-Finnish (FIN) AF: 0.342 AC: 14134 AN: 41306

Middle Eastern (MID) AF: 0.427 AC: 1024 AN: 2400

European-Non Finnish (NFE) AF: 0.396 AC: 176238 AN: 444594

Other (OTH) AF: 0.408 AC: 13588 AN: 33274

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

African (AFR) AF: 0.506 AC: 20985 AN: 41434

American (AMR) AF: 0.479 AC: 7317 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.362 AC: 1257 AN: 3468

East Asian (EAS) AF: 0.438 AC: 2261 AN: 5162

South Asian (SAS) AF: 0.451 AC: 2169 AN: 4814

European-Finnish (FIN) AF: 0.348 AC: 3676 AN: 10572

Middle Eastern (MID) AF: 0.456 AC: 134 AN: 294

European-Non Finnish (NFE) AF: 0.393 AC: 26686 AN: 67964

Other (OTH) AF: 0.418 AC: 879 AN: 2102

Alfa AF: 0.423 Hom.: 10662

Bravo AF: 0.445

Asia WGS AF: 0.457 AC: 1590 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.5
DANN	Benign	0.54
PhyloP100		-0.0040
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: rs6444724; hg19: chr3-193207380; COSMIC: COSV55075785;