Genetic Variant NM_001353812.2:c.2732A>T (chrX-139750121-T-A) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_001353812.2(ATP11C):c.2732A>T(p.Tyr911Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000184 in 1,089,489 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.0000018 ( 0 hom. 0 hem. )

Consequence

ATP11C
NM_001353812.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.67

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.762

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001353812.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ATP11C	NM_001353812.2	MANE Select	c.2732A>T	p.Tyr911Phe	missense	Exon 24 of 30	NP_001340741.2	A0A804HIW2
ATP11C	NM_173694.5		c.2741A>T	p.Tyr914Phe	missense	Exon 24 of 30	NP_775965.3
ATP11C	NM_001353811.2		c.2732A>T	p.Tyr911Phe	missense	Exon 24 of 30	NP_001340740.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ATP11C	ENST00000682941.1	MANE Select	c.2732A>T	p.Tyr911Phe	missense	Exon 24 of 30	ENSP00000507250.1	A0A804HIW2
ATP11C	ENST00000327569.7	TSL:1	c.2741A>T	p.Tyr914Phe	missense	Exon 24 of 30	ENSP00000332756.3	Q8NB49-1
ATP11C	ENST00000361648.6	TSL:1	c.2741A>T	p.Tyr914Phe	missense	Exon 24 of 29	ENSP00000355165.2	Q8NB49-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000109

AC:

AN:

182691

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000733

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

0.00000184

AC:

AN:

1089489

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

355949

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26286

American (AMR)

AF:

0.0000569

AC:

AN:

35121

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19129

East Asian (EAS)

AF:

0.00

AC:

AN:

30132

South Asian (SAS)

AF:

0.00

AC:

AN:

52460

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40236

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4106

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

836334

Other (OTH)

AF:

0.00

AC:

AN:

45685

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000529

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.027

BayesDel_noAF

Benign

-0.090

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.14

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.96

M_CAP

Pathogenic

0.57

MetaRNN

Pathogenic

0.76

MetaSVM

Uncertain

0.46

MutationAssessor

Benign

0.64

PhyloP100

7.7

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

-2.3

REVEL

Pathogenic

0.69

Sift

Benign

0.29

Sift4G

Benign

0.27

Polyphen

1.0

Vest4

0.53

MutPred

0.75

Gain of glycosylation at T919 (P = 0.2103)

MVP

0.80

MPC

1.0

ClinPred

0.62

GERP RS

6.0

PromoterAI

-0.0054

Neutral

(source)

Varity_R

0.66

gMVP

0.52

Mutation Taster

=60/40

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over