dbSNP rs201052330: ATP11C:p.Tyr1033Phe (chrX-139741027-T-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001353812.2(ATP11C):c.3098A>T(p.Tyr1033Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000332 in 1,204,641 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y1033C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000090 ( 0 hom., 0 hem., cov: 22)

Exomes 𝑓: 0.0000027 ( 0 hom. 1 hem. )

Consequence

ATP11C
NM_001353812.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.63

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

X-linked congenital hemolytic anemia
Inheritance: XL, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ATP11C links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.23248634).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP11C	NM_001353812.2 link	c.3098A>T	p.Tyr1033Phe	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.3098A>T	p.Tyr1033Phe	missense_variant	Exon 27 of 30		NM_001353812.2	ENSP00000507250.1		A0A804HIW2

Frequencies

GnomAD3 genomes

AF:

0.00000897

AC:

AN:

111506

Hom.:

Cov.:

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000167

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000548

AC:

AN:

182376

AF XY:

0.00

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 FIN exome

AF:

0.0000627

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1093081

Hom.:

Cov.:

AF XY:

0.00000278

AC XY:

AN XY:

359267

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26241

American (AMR)

AF:

0.00

AC:

AN:

35054

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19297

East Asian (EAS)

AF:

0.00

AC:

AN:

30162

South Asian (SAS)

AF:

0.00

AC:

AN:

53971

European-Finnish (FIN)

AF:

0.0000741

AC:

AN:

40487

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4114

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

837889

Other (OTH)

AF:

0.00

AC:

AN:

45866

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000896

AC:

AN:

111560

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33828

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30757

American (AMR)

AF:

0.00

AC:

AN:

10494

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2634

East Asian (EAS)

AF:

0.00

AC:

AN:

3518

South Asian (SAS)

AF:

0.00

AC:

AN:

2650

European-Finnish (FIN)

AF:

0.000167

AC:

AN:

6003

Middle Eastern (MID)

AF:

0.00

AC:

AN:

217

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53075

Other (OTH)

AF:

0.00

AC:

AN:

1529

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.094

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.097

.;T;.;.

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.99

D;D;D;D

M_CAP

Uncertain

0.24

MetaRNN

Benign

0.23

T;T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Uncertain

2.2

.;M;M;.

PhyloP100

7.6

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-1.5

N;N;N;D

REVEL

Benign

0.16

Sift

Benign

0.29

T;T;T;T

Sift4G

Benign

0.36

T;T;T;T

Polyphen

0.39, 0.53

.;B;P;.

Vest4

0.52

MVP

0.42

MPC

1.3

ClinPred

0.61

GERP RS

5.5

Varity_R

0.78

gMVP

0.76

Mutation Taster

=56/44

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over