chr3-194406320-C-T

Variant names:

• chr3-194406320-C-T
• rs13324377
• NM_001367549.1:c.3574-204G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001367549.1(ATP13A3):​c.3574-204G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.369 in 151,956 control chromosomes in the GnomAD database, including 14,484 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.37 (14484 hom., cov: 32)
• Consequence: ATP13A3 NM_001367549.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.03
• Publications: 2 publications found

Genes affected

ATP13A3 (HGNC:24113): (ATPase 13A3) ATP13A3 is a member of the P-type ATPase family of proteins that transport a variety of cations across membranes. Other P-type ATPases include ATP7B (MIM 606882) and ATP7A (MIM 300011).[supplied by OMIM, Aug 2008]

ATP13A3 Gene-Disease associations (from GenCC):

• pulmonary arterial hypertension

  Inheritance: SD Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BP6: Variant 3-194406320-C-T is Benign according to our data. Variant chr3-194406320-C-T is described in ClinVar as Benign. ClinVar VariationId is 1252466.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.73 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001367549.1. 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
	ATP13A3	NM_001367549.1	MANE Select	c.3574-204G>A		intron	N/A	NP_001354478.1	A0A2R8Y635
	ATP13A3	NM_001374836.1		c.3493-204G>A		intron	N/A	NP_001361765.1
	ATP13A3	NM_001437993.1		c.3484-204G>A		intron	N/A	NP_001424922.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP13A3	ENST00000645319.2	MANE Select	c.3574-204G>A		intron	N/A	ENSP00000494937.2	A0A2R8Y635
	ATP13A3	ENST00000429136.7	TSL:1	n.1420-204G>A		intron	N/A
	ATP13A3	ENST00000461660.2	TSL:1	n.678-204G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.369 AC: 55967 AN: 151838 Hom.: 14438 Cov.: 32

Gnomad AFR AF: 0.737

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.270

Gnomad EAS AF: 0.287

Gnomad SAS AF: 0.379

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.204

Gnomad OTH AF: 0.367

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

GnomAD4 genome AF: 0.369 AC: 56066 AN: 151956 Hom.: 14484 Cov.: 32 AF XY: 0.367 AC XY: 27276 AN XY: 74276

African (AFR) AF: 0.737 AC: 30529 AN: 41408

American (AMR) AF: 0.268 AC: 4101 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.270 AC: 935 AN: 3466

East Asian (EAS) AF: 0.287 AC: 1481 AN: 5160

South Asian (SAS) AF: 0.379 AC: 1825 AN: 4816

European-Finnish (FIN) AF: 0.218 AC: 2301 AN: 10560

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.204 AC: 13846 AN: 67954

Other (OTH) AF: 0.366 AC: 772 AN: 2112

Alfa AF: 0.282 Hom.: 1084

Bravo AF: 0.390

Asia WGS AF: 0.370 AC: 1288 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.73
DANN	Benign	0.47
PhyloP100		-1.0
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: rs13324377; hg19: chr3-194127049; COSMIC: COSV107308278;