Variant X-139745823-G-A 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_001353812.2(ATP11C):c.2863C>T(p.Pro955Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000223 in 1,202,634 control chromosomes in the GnomAD database, including 1 homozygotes. There are 84 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000080 ( 0 hom., 4 hem., cov: 23)

Exomes 𝑓: 0.00024 ( 1 hom. 80 hem. )

Consequence

ATP11C
NM_001353812.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.63

Variant links:

Genes affected

ATP11C (HGNC:13554): (ATPase phospholipid transporting 11C) Enables phosphatidylethanolamine flippase activity and phosphatidylserine flippase activity. Predicted to be involved in phospholipid translocation; positive regulation of B cell differentiation; and pre-B cell differentiation. Located in endoplasmic reticulum and plasma membrane. Is integral component of plasma membrane. Implicated in X-linked congenital hemolytic anemia. [provided by Alliance of Genome Resources, Apr 2022]

ATP11C 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=0.093842804).

BS2

High Hemizygotes in GnomAd4 at 4 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP11C	NM_001353812.2 linkuse as main transcript	c.2863C>T	p.Pro955Ser	missense_variant	25/30	ENST00000682941.1	NP_001340741.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP11C	ENST00000682941.1 linkuse as main transcript	c.2863C>T	p.Pro955Ser	missense_variant	25/30		NM_001353812.2	ENSP00000507250	A1

Frequencies

GnomAD3 genomes

AF:

0.0000804

AC:

AN:

111989

Hom.:

Cov.:

AF XY:

0.000117

AC XY:

AN XY:

34233

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00254

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:

0.000119

AC:

AN:

177117

Hom.:

AF XY:

0.0000805

AC XY:

AN XY:

62099

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00158

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000237

AC:

259

AN:

1090594

Hom.:

Cov.:

AF XY:

0.000224

AC XY:

AN XY:

356930

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00850

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000874

GnomAD4 genome

AF:

0.0000803

AC:

AN:

112040

Hom.:

Cov.:

AF XY:

0.000117

AC XY:

AN XY:

34294

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00255

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000422

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.000132

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 04, 2022

The c.2872C>T (p.P958S) alteration is located in exon 25 (coding exon 25) of the ATP11C gene. This alteration results from a C to T substitution at nucleotide position 2872, causing the proline (P) at amino acid position 958 to be replaced by a serine (S). 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

0.26

BayesDel_addAF

Uncertain

0.020

BayesDel_noAF

Pathogenic

0.23

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.11

.;T;.;.

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.92

D;D;D;D

M_CAP

Pathogenic

0.72

MetaRNN

Benign

0.094

T;T;T;T

MetaSVM

Uncertain

-0.26

MutationAssessor

Benign

0.17

.;N;N;.

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-1.6

N;N;N;N

REVEL

Uncertain

0.52

Sift

Benign

0.59

T;T;T;T

Sift4G

Benign

0.73

T;T;T;T

Polyphen

0.44, 0.57

.;B;P;.

Vest4

0.44

MutPred

0.43

.;Gain of catalytic residue at P958 (P = 0.0515);Gain of catalytic residue at P958 (P = 0.0515);.;

MVP

0.98

MPC

1.2

ClinPred

0.090

GERP RS

6.0

Varity_R

0.45

gMVP

0.79

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