13-112805044-C-G

Position:

• chr13-112805044-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3 PP5

The NM_015205.3(ATP11A):​c.250C>G​(p.Gln84Glu) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Pathogenic (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely pathogenicin UniProt.

• Frequency: Genomes: not found (cov: 30)
• Consequence: ATP11A NM_015205.3 missense, splice_region
• Scores: Splicing: ADA: 0.3394
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.08

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.815
• PP5: Variant 13-112805044-C-G is Pathogenic according to our data. Variant chr13-112805044-C-G is described in ClinVar as [Pathogenic]. Clinvar id is 1686851.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP11A	NM_015205.3	c.250C>G	p.Gln84Glu	missense_variant, splice_region_variant	3/30	ENST00000375645.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP11A	ENST00000375645.8	c.250C>G	p.Gln84Glu	missense_variant, splice_region_variant	3/30	5	NM_015205.3	P1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 30

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Leukodystrophy, hypomyelinating, 24 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

May 16, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.71
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Uncertain	0.13
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.12	T;T;T
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.96	D
M_CAP	Uncertain	0.14	D
MetaRNN	Pathogenic	0.82	D;D;D
MetaSVM	Uncertain	0.040	D
MutationAssessor	Pathogenic	2.9	M;M;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-2.3	N;N;N
REVEL	Pathogenic	0.66
Sift	Uncertain	0.0040	D;D;T
Sift4G	Benign	0.091	T;T;T
Polyphen		0.12	B;B;B
Vest4		0.78
MutPred		0.68		Gain of catalytic residue at L85 (P = 5e-04);Gain of catalytic residue at L85 (P = 5e-04);Gain of catalytic residue at L85 (P = 5e-04);
MVP		0.92
MPC		0.59
ClinPred		0.95	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.31
gMVP		0.93

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.34
dbscSNV1_RF	Benign	0.43
SpliceAI score (max)		0.16		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: chr13-113459358;