19-1783092-A-G

Position:

• chr19-1783092-A-G

Variant summary

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

The NM_138813.4(ATP8B3):​c.3839T>C​(p.Ile1280Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: ATP8B3 NM_138813.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.155

Genes affected

ATP8B3 (HGNC:13535): (ATPase phospholipid transporting 8B3) The protein encoded by this gene belongs to the family of P-type cation transport ATPases, and to the subfamily of aminophospholipid-transporting ATPases. The aminophospholipid translocases transport phosphatidylserine and phosphatidylethanolamine from one side of a bilayer to the other. This gene encodes member 3 of phospholipid-transporting ATPase 8B; other members of this protein family are located on chromosomes 1, 15 and 18. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]

ATP8B3 (HGNC:):

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=0.068656).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP8B3	NM_138813.4	c.3839T>C	p.Ile1280Thr	missense_variant	29/29	ENST00000310127.10	NP_620168.1
ATP8B3	NM_001178002.3	c.3728T>C	p.Ile1243Thr	missense_variant	29/29		NP_001171473.1
ATP8B3	NR_047593.3	n.4222T>C		non_coding_transcript_exon_variant	29/29

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP8B3	ENST00000310127.10	c.3839T>C	p.Ile1280Thr	missense_variant	29/29	1	NM_138813.4	ENSP00000311336.6
ATP8B3	ENST00000525591.5	c.3728T>C	p.Ile1243Thr	missense_variant	29/29	1		ENSP00000437115.1
ATP8B3	ENST00000531925.5	n.*3722T>C		non_coding_transcript_exon_variant	29/29	2		ENSP00000444334.1
ATP8B3	ENST00000531925.5	n.*3722T>C		3_prime_UTR_variant	29/29	2		ENSP00000444334.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 08, 2024

The c.3839T>C (p.I1280T) alteration is located in exon 29 (coding exon 28) of the ATP8B3 gene. This alteration results from a T to C substitution at nucleotide position 3839, causing the isoleucine (I) at amino acid position 1280 to be replaced by a threonine (T). 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	0.065
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.68
DANN	Benign	0.63
DEOGEN2	Benign	0.040	T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.36	T;T
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.069	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N;.
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.31	N;N
REVEL	Benign	0.023
Sift	Benign	0.38	T;T
Sift4G	Benign	0.40	T;T
Polyphen		0.0	B;.
Vest4		0.011
MutPred		0.32		Loss of stability (P = 0.0188);.;
MVP		0.25
MPC		0.097
ClinPred		0.099	T
GERP RS		-1.0
Varity_R		0.032
gMVP		0.25

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: chr19-1783091;