chrX-139738013-A-C

Variant names:

• chrX-139738013-A-C
• rs890191882
• NM_001353812.2:c.3191T>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001353812.2(ATP11C):​c.3191T>G​(p.Val1064Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: ATP11C NM_001353812.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.34
• Publications: 0 publications found

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)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26870996).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP11C	NM_001353812.2	MANE Select	c.3191T>G	p.Val1064Gly	missense	Exon 28 of 30	NP_001340741.2	A0A804HIW2
	ATP11C	NM_173694.5		c.3200T>G	p.Val1067Gly	missense	Exon 28 of 30	NP_775965.3
	ATP11C	NM_001353811.2		c.3191T>G	p.Val1064Gly	missense	Exon 28 of 30	NP_001340740.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP11C	ENST00000682941.1	MANE Select	c.3191T>G	p.Val1064Gly	missense	Exon 28 of 30	ENSP00000507250.1	A0A804HIW2
	ATP11C	ENST00000327569.7	TSL:1	c.3200T>G	p.Val1067Gly	missense	Exon 28 of 30	ENSP00000332756.3	Q8NB49-1
	ATP11C	ENST00000361648.6	TSL:1	c.3200T>G	p.Val1067Gly	missense	Exon 28 of 29	ENSP00000355165.2	Q8NB49-3

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 23

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Benign	19
DANN	Benign	0.87
DEOGEN2	Benign	0.028	T
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.42	T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.27	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.68	N
PhyloP100		3.3
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	1.1	N
REVEL	Benign	0.25
Sift	Benign	0.33	T
Sift4G	Benign	0.63	T
Polyphen		0.0040	B
Vest4		0.31
MutPred		0.63		Loss of stability (P = 0.0051)
MVP		0.92
MPC		1.4
ClinPred		0.63	D
GERP RS		6.0
Varity_R		0.71
gMVP		0.76
Mutation Taster		=49/51	disease causing

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

Other links and lift over

dbSNP: rs890191882; hg19: chrX-138820172;