NM_014616.3:c.1306C>T

Variant names:

• chr3-182865561-C-T
• rs201531019
• NM_014616.3:c.1306C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_014616.3(ATP11B):​c.1306C>T​(p.Leu436Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,590 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. L436V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ATP11B NM_014616.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.59
• Publications: 2 publications found

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]

ENSG00000308148 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014616.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP11B	NM_014616.3	MANE Select	c.1306C>T	p.Leu436Phe	missense	Exon 13 of 30	NP_055431.1	Q9Y2G3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP11B	ENST00000323116.10	TSL:2 MANE Select	c.1306C>T	p.Leu436Phe	missense	Exon 13 of 30	ENSP00000321195.5	Q9Y2G3
	ATP11B	ENST00000868398.1		c.1306C>T	p.Leu436Phe	missense	Exon 13 of 31	ENSP00000538457.1
	ATP11B	ENST00000954648.1		c.1306C>T	p.Leu436Phe	missense	Exon 13 of 31	ENSP00000624707.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251304 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461590 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727094

African (AFR) AF: 0.00 AC: 0 AN: 33462

American (AMR) AF: 0.0000224 AC: 1 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39622

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111858

Other (OTH) AF: 0.00 AC: 0 AN: 60380

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Uncertain	0.031	T
BayesDel_noAF	Benign	-0.11
CADD	Uncertain	26
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.030	T
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.97	D
M_CAP	Benign	0.050	D
MetaRNN	Uncertain	0.44	T
MetaSVM	Uncertain	-0.23	T
MutationAssessor	Benign	1.9	L
PhyloP100		5.6
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-2.0	N
REVEL	Uncertain	0.30
Sift	Uncertain	0.0050	D
Sift4G	Benign	0.063	T
Polyphen		1.0	D
Vest4		0.42
MutPred		0.38		Loss of helix (P = 0.0558)
MVP		0.57
MPC		0.33
ClinPred		0.60	D
GERP RS		5.0
Varity_R		0.17
gMVP		0.45
Mutation Taster		=65/35	polymorphism

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

Other links and lift over

dbSNP: rs201531019; hg19: chr3-182583349;