Variant X-139741078-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001353812.2(ATP11C):c.3047G>A(p.Arg1016Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000101 in 1,087,054 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.000010 ( 0 hom. 4 hem. )

Consequence

ATP11C
NM_001353812.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.48

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 -4 ACMG points.

BS2

High Hemizygotes in GnomAdExome4 at 4 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP11C	NM_001353812.2 link	c.3047G>A	p.Arg1016Gln	missense_variant	Exon 27 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.3047G>A	p.Arg1016Gln	missense_variant	Exon 27 of 30		NM_001353812.2	ENSP00000507250.1		A0A804HIW2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000330

AC:

AN:

181563

Hom.:

AF XY:

0.0000301

AC XY:

AN XY:

66453

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000369

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000146

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000126

Gnomad NFE exome

AF:

0.0000123

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000101

AC:

AN:

1087054

Hom.:

Cov.:

AF XY:

0.0000113

AC XY:

AN XY:

353452

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000286

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000996

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000124

Gnomad4 NFE exome

AF:

0.00000240

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000825

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 06, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.3056G>A (p.R1019Q) alteration is located in exon 27 (coding exon 27) of the ATP11C gene. This alteration results from a G to A substitution at nucleotide position 3056, causing the arginine (R) at amino acid position 1019 to be replaced by a glutamine (Q). 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

0.17

BayesDel_addAF

Pathogenic

0.29

BayesDel_noAF

Pathogenic

0.17

CADD

Benign

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.068

.;T;.;.

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.92

D;D;D;D

M_CAP

Pathogenic

0.62

MetaRNN

Uncertain

0.47

T;T;T;T

MetaSVM

Uncertain

0.32

MutationAssessor

Benign

1.4

.;L;L;.

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-0.91

N;N;N;N

REVEL

Uncertain

0.64

Sift

Benign

0.16

T;T;T;D

Sift4G

Benign

0.32

T;T;T;T

Polyphen

0.99, 0.99

.;D;D;.

Vest4

0.50

MutPred

0.56

.;Loss of MoRF binding (P = 0.034);Loss of MoRF binding (P = 0.034);.;

MVP

0.99

MPC

1.4

ClinPred

0.58

GERP RS

3.8

Varity_R

0.45

gMVP

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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