Variant 13-112785139-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_015205.3(ATP11A):c.44C>T(p.Ala15Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000974 in 1,539,764 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000086 ( 0 hom. )

Consequence

ATP11A
NM_015205.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.00

Variant links:

Genes affected

ATP11A (HGNC:13552): (ATPase phospholipid transporting 11A) The protein encoded by this gene is an integral membrane ATPase. The encoded protein is probably phosphorylated in its intermediate state and likely drives the transport of ions such as calcium across membranes. [provided by RefSeq, Apr 2022]

ATP11A links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.13575166).

BS2

High AC in GnomAdExome4 at 12 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP11A	NM_015205.3 link	c.44C>T	p.Ala15Val	missense_variant	2/30	ENST00000375645.8	NP_056020.2	P98196Q659C3Q6PJ25

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP11A	ENST00000375645.8 link	c.44C>T	p.Ala15Val	missense_variant	2/30	5	NM_015205.3	ENSP00000364796.3		P98196

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD4 exome

AF:

0.00000865

AC:

AN:

1387590

Hom.:

Cov.:

AF XY:

0.00000727

AC XY:

AN XY:

687874

show subpopulations

Gnomad4 AFR exome

AF:

0.000201

Gnomad4 AMR exome

AF:

0.0000308

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000464

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152174

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000478

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 13, 2024

The c.44C>T (p.A15V) alteration is located in exon 2 (coding exon 2) of the ATP11A gene. This alteration results from a C to T substitution at nucleotide position 44, causing the alanine (A) at amino acid position 15 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.024

T;T;T

Eigen

Benign

0.014

Eigen_PC

Benign

0.16

FATHMM_MKL

Uncertain

0.79

LIST_S2

Uncertain

0.95

.;D;D

M_CAP

Benign

0.016

MetaRNN

Benign

0.14

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.080

N;N;.

PrimateAI

Uncertain

0.79

PROVEAN

Benign

-1.1

N;N;N

REVEL

Benign

0.076

Sift

Benign

0.092

T;T;T

Sift4G

Benign

0.22

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.30

MutPred

0.43

Gain of catalytic residue at W20 (P = 0.0014);Gain of catalytic residue at W20 (P = 0.0014);Gain of catalytic residue at W20 (P = 0.0014);

MVP

0.26

MPC

0.29

ClinPred

0.13

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.21

gMVP

0.46

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over