3-182820329-C-T

Variant names:

• chr3-182820329-C-T
• NM_014616.3:c.97C>T

Variant summary

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

The NM_014616.3(ATP11B):​c.97C>T​(p.Leu33Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,362 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: ATP11B NM_014616.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.66

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=0.1942968).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP11B	NM_014616.3	c.97C>T	p.Leu33Phe	missense_variant	Exon 2 of 30	ENST00000323116.10	NP_055431.1
ATP11B	XM_047447784.1	c.97C>T	p.Leu33Phe	missense_variant	Exon 2 of 30		XP_047303740.1
ATP11B	XM_011512593.3	c.97C>T	p.Leu33Phe	missense_variant	Exon 2 of 31		XP_011510895.1
ATP11B	XM_011512594.3	c.97C>T	p.Leu33Phe	missense_variant	Exon 2 of 30		XP_011510896.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP11B	ENST00000323116.10	c.97C>T	p.Leu33Phe	missense_variant	Exon 2 of 30	2	NM_014616.3	ENSP00000321195.5
ATP11B	ENST00000493826.1	c.97C>T	p.Leu33Phe	missense_variant	Exon 2 of 6	1		ENSP00000419032.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461362 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 727034

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

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: 0.00

Gnomad4 OTH exome AF: 0.0000497

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 26, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.97C>T (p.L33F) alteration is located in exon 2 (coding exon 2) of the ATP11B gene. This alteration results from a C to T substitution at nucleotide position 97, causing the leucine (L) at amino acid position 33 to be replaced by a phenylalanine (F). 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	Benign	0.074
BayesDel_addAF	Benign	-0.089	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	24
DANN	Benign	0.97
DEOGEN2	Benign	0.0071	T;T
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.94	D;D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.19	T;T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	1.5	L;.
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-1.0	N;N
REVEL	Benign	0.13
Sift	Benign	0.15	T;T
Sift4G	Benign	0.71	T;T
Polyphen		0.012	B;.
Vest4		0.21
MutPred		0.35		Loss of catalytic residue at L33 (P = 0.097);Loss of catalytic residue at L33 (P = 0.097);
MVP		0.41
MPC		0.79
ClinPred		0.49	T
GERP RS		6.1
Varity_R		0.064
gMVP		0.62

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-182538117;