X-139750058-A-G

Variant names:

• chrX-139750058-A-G
• NM_001353812.2:c.2795T>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001353812.2(ATP11C):​c.2795T>C​(p.Ile932Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000917 in 1,090,874 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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: 5.98

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22088861).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP11C	NM_001353812.2	c.2795T>C	p.Ile932Thr	missense_variant	Exon 24 of 30	ENST00000682941.1	NP_001340741.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP11C	ENST00000682941.1	c.2795T>C	p.Ile932Thr	missense_variant	Exon 24 of 30		NM_001353812.2	ENSP00000507250.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.17e-7 AC: 1 AN: 1090874 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 357084

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: 0.0000189

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

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

Dec 12, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2804T>C (p.I935T) alteration is located in exon 24 (coding exon 24) of the ATP11C gene. This alteration results from a T to C substitution at nucleotide position 2804, causing the isoleucine (I) at amino acid position 935 to be replaced by a threonine (T). 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	Benign	0.14
BayesDel_addAF	Benign	-0.047	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	21
DANN	Benign	0.92
DEOGEN2	Benign	0.047	.;T;.
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.84	T;T;T
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.22	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	.;L;L
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.90	N;N;N
REVEL	Benign	0.11
Sift	Benign	0.56	T;T;T
Sift4G	Benign	0.55	T;T;T
Polyphen		0.048, 0.081	.;B;B
Vest4		0.38
MutPred		0.42		.;Loss of stability (P = 0.0012);Loss of stability (P = 0.0012);
MVP		0.59
MPC		1.3
ClinPred		0.78	D
GERP RS		5.9
Varity_R		0.73
gMVP		0.32

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-138832217;