Variant 13-112690427-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP5BP4

The NM_015205.3(ATP11A):c.11G>A(p.Ser4Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000838 in 1,192,922 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 Pathogenic (no stars).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 8.4e-7 ( 0 hom. )

Consequence

ATP11A
NM_015205.3 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 1.96

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 13-112690427-G-A is Pathogenic according to our data. Variant chr13-112690427-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 1527862.Status of the report is no_assertion_criteria_provided, 0 stars.

BP4

Computational evidence support a benign effect (MetaRNN=0.17626172). . Strength limited to SUPPORTING due to the PP5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP11A	NM_015205.3 link	c.11G>A	p.Ser4Asn	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.11G>A	p.Ser4Asn	missense_variant	1/30	5	NM_015205.3	ENSP00000364796.3	P98196
ATP11A	ENST00000375630.6 link	c.11G>A	p.Ser4Asn	missense_variant	1/29	5		ENSP00000364781.2	E9PEJ6
ATP11A	ENST00000487903.5 link	c.11G>A	p.Ser4Asn	missense_variant	1/30	5		ENSP00000420387.1	P98196

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

8.38e-7

AC:

AN:

1192922

Hom.:

Cov.:

AF XY:

0.00000172

AC XY:

AN XY:

580710

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000229

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Hearing loss, autosomal dominant 84

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

May 24, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.016

T;T;T

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.14

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.61

.;T;T

M_CAP

Pathogenic

0.47

MetaRNN

Benign

0.18

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

L;L;.

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-0.27

N;N;N

REVEL

Benign

0.073

Sift

Uncertain

0.023

D;D;D

Sift4G

Benign

0.37

T;T;T

Polyphen

0.019

B;B;B

Vest4

0.26

MutPred

0.30

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

0.38

MPC

0.28

ClinPred

0.21

GERP RS

3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.093

gMVP

0.66

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over