13-112690448-A-C

Position:

• chr13-112690448-A-C

Variant summary

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

The NM_015205.3(ATP11A):​c.32A>C​(p.His11Pro) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ATP11A NM_015205.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0260

Genes affected

ATP11A (HGNC:13552): (ATPase phospholipid transporting 11A) The protein encoded by this gene is an integral membrane ATPase. The encoded protein is probably phosphorylated in its intermediate state and likely drives the transport of ions such as calcium across membranes. [provided by RefSeq, 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=0.09754774).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP11A	NM_015205.3	c.32A>C	p.His11Pro	missense_variant	1/30	ENST00000375645.8	NP_056020.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP11A	ENST00000375645.8	c.32A>C	p.His11Pro	missense_variant	1/30	5	NM_015205.3	ENSP00000364796.3
ATP11A	ENST00000375630.6	c.32A>C	p.His11Pro	missense_variant	1/29	5		ENSP00000364781.2
ATP11A	ENST00000487903.5	c.32A>C	p.His11Pro	missense_variant	1/30	5		ENSP00000420387.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 14, 2024

The c.32A>C (p.H11P) alteration is located in exon 1 (coding exon 1) of the ATP11A gene. This alteration results from a A to C substitution at nucleotide position 32, causing the histidine (H) at amino acid position 11 to be replaced by a proline (P). 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	0.098
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	17
DANN	Benign	0.91
DEOGEN2	Benign	0.019	T;T;T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.46
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.56	.;T;T
M_CAP	Uncertain	0.27	D
MetaRNN	Benign	0.098	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N;N;.
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-1.0	N;N;N
REVEL	Benign	0.089
Sift	Benign	0.16	T;T;T
Sift4G	Benign	0.18	T;T;T
Polyphen		0.011	B;B;B
Vest4		0.22
MutPred		0.49		Gain of catalytic residue at R12 (P = 0.0056);Gain of catalytic residue at R12 (P = 0.0056);Gain of catalytic residue at R12 (P = 0.0056);
MVP		0.26
MPC		0.46
ClinPred		0.061	T
GERP RS		0.96
Varity_R		0.25
gMVP		0.70

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: chr13-113344762;