X-139768298-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001353812.2(ATP11C):c.2353G>T(p.Val785Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: ATP11C NM_001353812.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.57

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.865

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP11C	NM_001353812.2	c.2353G>T	p.Val785Leu	missense_variant	20/30	ENST00000682941.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP11C	ENST00000682941.1	c.2353G>T	p.Val785Leu	missense_variant	20/30		NM_001353812.2	A1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1054738 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 332508

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 22

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

X-linked congenital hemolytic anemia Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Revvity Omics, Revvity

Jun 08, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.84
BayesDel_addAF	Pathogenic	0.33	D
BayesDel_noAF	Pathogenic	0.23
Cadd	Uncertain	26
Dann	Uncertain	1.0
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.99	D;D;D
M_CAP	Pathogenic	0.34	D
MetaRNN	Pathogenic	0.87	D;D;D
MetaSVM	Pathogenic	0.90	D
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.70	T
PROVEAN	Uncertain	-2.9	D;D;D
REVEL	Pathogenic	0.85
Sift	Pathogenic	0.0	D;D;D
Sift4G	Uncertain	0.0030	D;D;D
Polyphen		1.0	.;D;D
Vest4		0.64
MutPred		0.82		.;Loss of catalytic residue at V788 (P = 0.0325);Loss of catalytic residue at V788 (P = 0.0325);
MVP		0.96
MPC		1.0
ClinPred		1.0	D
GERP RS		4.5
Varity_R		0.94
gMVP		0.86

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-138850457;