X-139745781-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001353812.2(ATP11C):c.2905G>A(p.Val969Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00495 in 1,206,478 control chromosomes in the GnomAD database, including 177 homozygotes. There are 1,552 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.026 ( 101 hom., 741 hem., cov: 23)

Exomes 𝑓: 0.0028 ( 76 hom. 811 hem. )

Consequence

ATP11C
NM_001353812.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.96

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 was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0055324733).

BP6

Variant X-139745781-C-T is Benign according to our data. Variant chrX-139745781-C-T is described in ClinVar as [Benign]. Clinvar id is 783916.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0846 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP11C	NM_001353812.2 link	c.2905G>A	p.Val969Met	missense_variant	Exon 25 of 30	ENST00000682941.1	NP_001340741.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP11C	ENST00000682941.1 link	c.2905G>A	p.Val969Met	missense_variant	Exon 25 of 30		NM_001353812.2	ENSP00000507250.1		A0A804HIW2

Frequencies

GnomAD3 genomes

AF:

0.0256

AC:

2864

AN:

112079

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0872

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0105

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00111

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0126

Gnomad NFE

AF:

0.000657

Gnomad OTH

AF:

0.0192

GnomAD2 exomes

AF:

0.00754

AC:

1361

AN:

180574

AF XY:

0.00446

show subpopulations

Gnomad AFR exome

AF:

0.0923

Gnomad AMR exome

AF:

0.00428

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000482

Gnomad OTH exome

AF:

0.00271

GnomAD4 exome

AF:

0.00284

AC:

3104

AN:

1094346

Hom.:

Cov.:

AF XY:

0.00225

AC XY:

811

AN XY:

360314

show subpopulations

African (AFR)

AF:

0.0895

AC:

2345

AN:

26199

American (AMR)

AF:

0.00520

AC:

182

AN:

35015

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19282

East Asian (EAS)

AF:

0.00

AC:

AN:

30106

South Asian (SAS)

AF:

0.000187

AC:

AN:

53477

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40462

Middle Eastern (MID)

AF:

0.00534

AC:

AN:

4120

European-Non Finnish (NFE)

AF:

0.000302

AC:

254

AN:

839760

Other (OTH)

AF:

0.00634

AC:

291

AN:

45925

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.451

Heterozygous variant carriers

104

208

313

417

521

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0256

AC:

2872

AN:

112132

Hom.:

101

Cov.:

AF XY:

0.0216

AC XY:

741

AN XY:

34350

show subpopulations

African (AFR)

AF:

0.0874

AC:

2694

AN:

30832

American (AMR)

AF:

0.0104

AC:

110

AN:

10585

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2654

East Asian (EAS)

AF:

0.00

AC:

AN:

3538

South Asian (SAS)

AF:

0.00111

AC:

AN:

2703

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6148

Middle Eastern (MID)

AF:

0.00461

AC:

AN:

217

European-Non Finnish (NFE)

AF:

0.000657

AC:

AN:

53238

Other (OTH)

AF:

0.0190

AC:

AN:

1530

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

104

208

312

416

520

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00775

Hom.:

362

Bravo

AF:

0.0297

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000692

AC:

ESP6500AA

AF:

0.0918

AC:

352

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00863

AC:

1047

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

ATP11C-related disorder

Benign:1

May 23, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.29

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

.;T;.;.

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.91

D;D;D;D

MetaRNN

Benign

0.0055

T;T;T;T

MetaSVM

Benign

-0.76

MutationAssessor

Uncertain

2.1

.;M;M;.

PhyloP100

2.0

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-2.2

N;N;N;N

REVEL

Uncertain

0.40

Sift

Uncertain

0.0010

D;D;D;D

Sift4G

Uncertain

0.0020

D;D;D;D

Polyphen

0.96, 0.97

.;D;D;.

Vest4

0.29

MVP

0.73

MPC

0.58

ClinPred

0.025

GERP RS

6.0

PromoterAI

-0.032

Neutral

(source)

Varity_R

0.61

gMVP

0.64

Mutation Taster

=96/4

polymorphism (auto)

(source)

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

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X-139745781-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over