3-182866289-T-G

Variant names:

• chr3-182866289-T-G
• rs150138064
• NM_014616.3:c.1465T>G

Variant summary

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

The NM_014616.3(ATP11B):​c.1465T>G​(p.Phe489Val) variant causes a missense change. The variant allele was found at a frequency of 0.000398 in 1,590,004 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00028 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00041 (1 hom.)
• Consequence: ATP11B NM_014616.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.31

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 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=0.25205064).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP11B	NM_014616.3	c.1465T>G	p.Phe489Val	missense_variant	Exon 14 of 30	ENST00000323116.10	NP_055431.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP11B	ENST00000323116.10	c.1465T>G	p.Phe489Val	missense_variant	Exon 14 of 30	2	NM_014616.3	ENSP00000321195.5
ATP11B	ENST00000498086.5	c.865T>G	p.Phe289Val	missense_variant	Exon 8 of 25	5		ENSP00000418421.1
ATP11B	ENST00000490303.5	n.194T>G		non_coding_transcript_exon_variant	Exon 2 of 17	2

Frequencies

GnomAD3 genomes AF: 0.000289 AC: 44 AN: 152216 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000573

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000251 AC: 60 AN: 239146 Hom.: 0 AF XY: 0.000263 AC XY: 34 AN XY: 129212

Gnomad AFR exome AF: 0.0000645

Gnomad AMR exome AF: 0.000286

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000250

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000374

Gnomad OTH exome AF: 0.000346

GnomAD4 exome AF: 0.000410 AC: 590 AN: 1437670 Hom.: 1 Cov.: 30 AF XY: 0.000402 AC XY: 287 AN XY: 714024

Gnomad4 AFR exome AF: 0.000123

Gnomad4 AMR exome AF: 0.000378

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000242

Gnomad4 FIN exome AF: 0.0000189

Gnomad4 NFE exome AF: 0.000458

Gnomad4 OTH exome AF: 0.000423

GnomAD4 genome AF: 0.000282 AC: 43 AN: 152334 Hom.: 0 Cov.: 32 AF XY: 0.000322 AC XY: 24 AN XY: 74492

Gnomad4 AFR AF: 0.0000240

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000573

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000407 Hom.: 0

Bravo AF: 0.000295

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000814 AC: 7

ExAC AF: 0.000214 AC: 26

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 18, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1465T>G (p.F489V) alteration is located in exon 14 (coding exon 14) of the ATP11B gene. This alteration results from a T to G substitution at nucleotide position 1465, causing the phenylalanine (F) at amino acid position 489 to be replaced by a valine (V). 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	Pathogenic	0.62
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.037	T
Eigen	Benign	0.078
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.046	D
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.66	T
MutationAssessor	Benign	1.7	L
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.20
Sift	Uncertain	0.020	D
Sift4G	Benign	0.18	T
Polyphen		0.16	B
Vest4		0.64
MVP		0.31
MPC		0.68
ClinPred		0.36	T
GERP RS		4.3
Varity_R		0.20
gMVP		0.50

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

LitVar

Other links and lift over

dbSNP: rs150138064; hg19: chr3-182584077;