chr1-16985990-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000341676.9(ATP13A2):​c.3472G>A​(p.Val1158Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000919 in 1,447,984 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0038 ( 3 hom., cov: 31)
Exomes 𝑓: 0.00058 ( 5 hom. )

Consequence

ATP13A2
ENST00000341676.9 missense

Scores

1
13

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.58
Variant links:
Genes affected
ATP13A2 (HGNC:30213): (ATPase cation transporting 13A2) This gene encodes a member of the P5 subfamily of ATPases which transports inorganic cations as well as other substrates. Mutations in this gene are associated with Kufor-Rakeb syndrome (KRS), also referred to as Parkinson disease 9. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Nov 2008]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.004043579).
BP6
Variant 1-16985990-C-T is Benign according to our data. Variant chr1-16985990-C-T is described in ClinVar as [Benign]. Clinvar id is 876291.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0038 (578/152208) while in subpopulation AFR AF= 0.0125 (517/41518). AF 95% confidence interval is 0.0116. There are 3 homozygotes in gnomad4. There are 252 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ATP13A2NM_022089.4 linkuse as main transcriptc.*231G>A 3_prime_UTR_variant 29/29 ENST00000326735.13

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ATP13A2ENST00000326735.13 linkuse as main transcriptc.*231G>A 3_prime_UTR_variant 29/291 NM_022089.4 A1Q9NQ11-1
ENST00000446261.1 linkuse as main transcriptn.187+6878C>T intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
AF:
0.00378
AC:
575
AN:
152090
Hom.:
3
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0124
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00131
Gnomad ASJ
AF:
0.00749
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000147
Gnomad OTH
AF:
0.00239
GnomAD3 exomes
AF:
0.00143
AC:
106
AN:
74308
Hom.:
0
AF XY:
0.00130
AC XY:
47
AN XY:
36188
show subpopulations
Gnomad AFR exome
AF:
0.0125
Gnomad AMR exome
AF:
0.000594
Gnomad ASJ exome
AF:
0.00804
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000688
Gnomad OTH exome
AF:
0.000945
GnomAD4 exome
AF:
0.000580
AC:
752
AN:
1295776
Hom.:
5
Cov.:
30
AF XY:
0.000525
AC XY:
329
AN XY:
627196
show subpopulations
Gnomad4 AFR exome
AF:
0.0133
Gnomad4 AMR exome
AF:
0.00111
Gnomad4 ASJ exome
AF:
0.00811
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000324
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000117
Gnomad4 OTH exome
AF:
0.00140
GnomAD4 genome
AF:
0.00380
AC:
578
AN:
152208
Hom.:
3
Cov.:
31
AF XY:
0.00339
AC XY:
252
AN XY:
74438
show subpopulations
Gnomad4 AFR
AF:
0.0125
Gnomad4 AMR
AF:
0.00131
Gnomad4 ASJ
AF:
0.00749
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000147
Gnomad4 OTH
AF:
0.00237
Alfa
AF:
0.00122
Hom.:
2
Bravo
AF:
0.00436
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000259
AC:
1
ExAC
AF:
0.000901
AC:
45

ClinVar

Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenApr 01, 2024ATP13A2: BP4, BS1, BS2 -
ATP13A2-related disorder Benign:1
Likely benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesAug 23, 2024This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Kufor-Rakeb syndrome Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJul 18, 2017This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.27
T
BayesDel_noAF
Benign
-0.15
CADD
Benign
0.24
DANN
Benign
0.92
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.4
FATHMM_MKL
Benign
0.0095
N
LIST_S2
Benign
0.56
T;T
MetaRNN
Benign
0.0040
T;T
MetaSVM
Benign
-0.32
T
MutationTaster
Benign
1.0
N;N;N
PROVEAN
Benign
-0.16
N;N
REVEL
Benign
0.26
Sift
Pathogenic
0.0
D;D
Sift4G
Benign
0.40
.;T
Vest4
0.23
MVP
0.42
ClinPred
0.0041
T
GERP RS
-6.7

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs76298930; hg19: chr1-17312485; API