X-139738051-C-G

Variant summary

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

The NM_001353812.2(ATP11C):c.3153G>C(p.Gln1051His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000921 in 1,085,926 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.2e-7 (0 hom. 0 hem.)
• Consequence: ATP11C NM_001353812.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.406

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/exons	MANE	UniProt
ATP11C	NM_001353812.2	c.3153G>C	p.Gln1051His	missense_variant	28/30	ENST00000682941.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP11C	ENST00000682941.1	c.3153G>C	p.Gln1051His	missense_variant	28/30		NM_001353812.2	A1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.21e-7 AC: 1 AN: 1085926 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 353504

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: 0.00000120

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 11, 2023

The c.3162G>C (p.Q1054H) alteration is located in exon 28 (coding exon 28) of the ATP11C gene. This alteration results from a G to C substitution at nucleotide position 3162, causing the glutamine (Q) at amino acid position 1054 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.81
BayesDel_addAF	Uncertain	0.040	T
BayesDel_noAF	Benign	-0.18
Cadd	Benign	20
Dann	Uncertain	0.99
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.96	D;D;D;D
M_CAP	Pathogenic	0.55	D
MetaRNN	Uncertain	0.50	T;T;T;T
MetaSVM	Benign	-0.92	T
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.79	T
PROVEAN	Uncertain	-3.0	D;D;D;D
REVEL	Benign	0.28
Sift	Uncertain	0.020	D;D;D;D
Sift4G	Benign	0.064	T;T;T;D
Polyphen		1.0	.;D;D;.
Vest4		0.57
MutPred		0.43		.;Loss of solvent accessibility (P = 0.0238);Loss of solvent accessibility (P = 0.0238);.;
MVP		0.67
MPC		1.3
ClinPred		0.98	D
GERP RS		3.9
Varity_R		0.91
gMVP		0.75

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-138820210;