rs778203393

Variant names:

• chr3-182848482-C-A
• NM_014616.3:c.776C>A

Your query was ambiguous. Multiple possible variants found:

• chr3-182848482-C-A
• chr3-182848482-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_014616.3(ATP11B):​c.776C>A​(p.Ala259Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000146 in 1,367,426 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A259V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: ATP11B NM_014616.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.51

Genes affected

ATP11B (HGNC:13553): (ATPase phospholipid transporting 11B (putative)) P-type ATPases, such as ATP11B, are phosphorylated in their intermediate state and drive uphill transport of ions across membranes. Several subfamilies of P-type ATPases have been identified. One subfamily transports heavy metal ions, such as Cu(2+) or Cd(2+). Another subfamily transports non-heavy metal ions, such as H(+), Na(+), K(+), or Ca(+). A third subfamily transports amphipaths, such as phosphatidylserine.[supplied by OMIM, Feb 2005]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.972

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP11B	NM_014616.3	c.776C>A	p.Ala259Glu	missense_variant	Exon 10 of 30	ENST00000323116.10	NP_055431.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP11B	ENST00000323116.10	c.776C>A	p.Ala259Glu	missense_variant	Exon 10 of 30	2	NM_014616.3	ENSP00000321195.5
ATP11B	ENST00000498086.5	c.176C>A	p.Ala59Glu	missense_variant	Exon 4 of 25	5		ENSP00000418421.1
ATP11B	ENST00000482794.1	n.663C>A		non_coding_transcript_exon_variant	Exon 7 of 7	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000146 AC: 2 AN: 1367426 Hom.: 0 Cov.: 27 AF XY: 0.00000147 AC XY: 1 AN XY: 678292

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000271

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: 9.43e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.49	D
BayesDel_noAF	Pathogenic	0.46
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Pathogenic	0.81	D
Eigen	Pathogenic	0.83
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Pathogenic	0.42	D
MetaRNN	Pathogenic	0.97	D
MetaSVM	Pathogenic	0.95	D
MutationAssessor	Pathogenic	3.3	M
PrimateAI	Pathogenic	0.85	D
PROVEAN	Pathogenic	-4.7	D
REVEL	Pathogenic	0.91
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.92
MutPred		0.79		Loss of MoRF binding (P = 0.048);
MVP		0.96
MPC		1.9
ClinPred		1.0	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.90
gMVP		0.96

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: chr3-182566270;