Variant 13-112690429-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.13C>T(p.Leu5Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000743 in 1,346,260 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 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

ATP11A
NM_015205.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.847

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.08272624).

BS2

High AC in GnomAdExome4 at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP11A	NM_015205.3 link	c.13C>T	p.Leu5Phe	missense_variant	1/30	ENST00000375645.8	NP_056020.2	P98196Q659C3Q6PJ25

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ATP11A	ENST00000375645.8 link	c.13C>T	p.Leu5Phe	missense_variant	1/30	5	NM_015205.3	ENSP00000364796.3	P98196
ATP11A	ENST00000375630.6 link	c.13C>T	p.Leu5Phe	missense_variant	1/29	5		ENSP00000364781.2	E9PEJ6
ATP11A	ENST00000487903.5 link	c.13C>T	p.Leu5Phe	missense_variant	1/30	5		ENSP00000420387.1	P98196

Frequencies

GnomAD3 genomes

AF:

0.00000659

AC:

AN:

151770

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.00

GnomAD3 exomes

AF:

0.0000135

AC:

AN:

74254

Hom.:

AF XY:

0.0000233

AC XY:

AN XY:

42962

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000104

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000753

AC:

AN:

1194490

Hom.:

Cov.:

AF XY:

0.00000860

AC XY:

AN XY:

581614

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000246

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000227

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000409

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000659

AC:

AN:

151770

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74128

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

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:

0.00

Bravo

AF:

0.0000151

ExAC

AF:

0.0000178

AC:

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 12, 2024

The c.13C>T (p.L5F) alteration is located in exon 1 (coding exon 1) of the ATP11A gene. This alteration results from a C to T substitution at nucleotide position 13, causing the leucine (L) at amino acid position 5 to be replaced by a phenylalanine (F). 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

0.060

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.015

T;T;T

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.23

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.65

.;T;T

M_CAP

Pathogenic

0.60

MetaRNN

Benign

0.083

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

L;L;.

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-0.44

N;N;N

REVEL

Benign

0.16

Sift

Benign

0.039

D;D;D

Sift4G

Benign

0.75

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.18

MutPred

0.55

Gain of catalytic residue at M1 (P = 0);Gain of catalytic residue at M1 (P = 0);Gain of catalytic residue at M1 (P = 0);

MVP

0.20

MPC

0.32

ClinPred

0.058

GERP RS

2.5

Varity_R

0.076

gMVP

0.51

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.

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