dbSNP rs1295591659: ATP11C:p.Trp1067* (chrX-139738003-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001353812.2(ATP11C):c.3201G>A(p.Trp1067*) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000916 in 1,091,754 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (no stars). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 9.2e-7 ( 0 hom. 1 hem. )

Consequence

ATP11C
NM_001353812.2 stop_gained

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 7.57

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP11C	NM_001353812.2 link	c.3201G>A	p.Trp1067*	stop_gained	Exon 28 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.3201G>A	p.Trp1067*	stop_gained	Exon 28 of 30		NM_001353812.2	ENSP00000507250.1		A0A804HIW2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000553

AC:

AN:

180754

AF XY:

0.0000152

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000372

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:

9.16e-7

AC:

AN:

1091754

Hom.:

Cov.:

AF XY:

0.00000279

AC XY:

AN XY:

358168

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26185

American (AMR)

AF:

0.0000286

AC:

AN:

34984

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19229

East Asian (EAS)

AF:

0.00

AC:

AN:

30098

South Asian (SAS)

AF:

0.00

AC:

AN:

53404

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40413

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4106

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

837512

Other (OTH)

AF:

0.00

AC:

AN:

45823

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ATP11C-related disorder

Uncertain:1

Jun 26, 2024

PreventionGenetics, part of Exact Sciences

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:clinical testing

The ATP11C c.3210G>A variant is predicted to result in premature protein termination (p.Trp1070*). To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0037% of alleles in individuals of Latino descent in gnomAD, including one hemizygous individual. Although we suspect that this variant may be pathogenic, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.54

BayesDel_noAF

Pathogenic

0.66

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

FATHMM_MKL

Pathogenic

0.99

PhyloP100

7.6

Vest4

0.43

ClinPred

0.98

GERP RS

5.8

Mutation Taster

=146/54

disease causing (fs/PTC)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over