X-139745823-G-C

Variant names:

• chrX-139745823-G-C
• rs756953682
• NM_001353812.2:c.2863C>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001353812.2(ATP11C):​c.2863C>G​(p.Pro955Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 23)
• Consequence: ATP11C NM_001353812.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.63

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 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	c.2863C>G	p.Pro955Ala	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	c.2863C>G	p.Pro955Ala	missense_variant	Exon 25 of 30		NM_001353812.2	ENSP00000507250.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 23

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.17
CADD	Benign	22
DANN	Benign	0.49
DEOGEN2	Benign	0.11	.;T;.;.
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.91	D;D;D;D
M_CAP	Pathogenic	0.59	D
MetaRNN	Uncertain	0.47	T;T;T;T
MetaSVM	Benign	-0.33	T
MutationAssessor	Benign	0.19	.;N;N;.
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-1.8	N;N;N;N
REVEL	Uncertain	0.45
Sift	Benign	0.92	T;T;T;T
Sift4G	Benign	0.76	T;T;T;T
Polyphen		0.021, 0.036	.;B;B;.
Vest4		0.30
MutPred		0.40		.;Gain of catalytic residue at P958 (P = 0.028);Gain of catalytic residue at P958 (P = 0.028);.;
MVP		0.98
MPC		0.98
ClinPred		0.52	D
GERP RS		6.0
Varity_R		0.47
gMVP		0.69

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

LitVar

Other links and lift over

dbSNP: rs756953682; hg19: chrX-138827982;