3-182837092-A-G

Variant names:

• chr3-182837092-A-G
• NM_014616.3:c.574A>G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_014616.3(ATP11B):​c.574A>G​(p.Thr192Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ATP11B NM_014616.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.47

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.88

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP11B	NM_014616.3	c.574A>G	p.Thr192Ala	missense_variant	Exon 7 of 30	ENST00000323116.10	NP_055431.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP11B	ENST00000323116.10	c.574A>G	p.Thr192Ala	missense_variant	Exon 7 of 30	2	NM_014616.3	ENSP00000321195.5
ATP11B	ENST00000482794.1	n.461A>G		non_coding_transcript_exon_variant	Exon 4 of 7	5
ATP11B	ENST00000498086.5	c.-27A>G		upstream_gene_variant		5		ENSP00000418421.1

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

not specified Uncertain:1

Oct 22, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.574A>G (p.T192A) alteration is located in exon 7 (coding exon 7) of the ATP11B gene. This alteration results from a A to G substitution at nucleotide position 574, causing the threonine (T) at amino acid position 192 to be replaced by an alanine (A). 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	0.61
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.62	D
Eigen	Pathogenic	0.89
Eigen_PC	Pathogenic	0.83
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.69	T
M_CAP	Uncertain	0.25	D
MetaRNN	Pathogenic	0.88	D
MetaSVM	Pathogenic	0.93	D
MutationAssessor	Pathogenic	3.2	M
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-3.9	D
REVEL	Pathogenic	0.86
Sift	Benign	0.052	T
Sift4G	Uncertain	0.026	D
Polyphen		0.99	D
Vest4		0.57
MutPred		0.72		Loss of sheet (P = 0.302);
MVP		0.84
MPC		1.7
ClinPred		0.99	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.30
gMVP		0.65

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: chr3-182554880;