19-1783119-C-G

Variant names:

• chr19-1783119-C-G
• NM_138813.4:c.3812G>C

Variant summary

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

The NM_138813.4(ATP8B3):​c.3812G>C​(p.Arg1271Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: 4.16

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP8B3	NM_138813.4	c.3812G>C	p.Arg1271Pro	missense_variant	Exon 29 of 29	ENST00000310127.10	NP_620168.1
ATP8B3	NM_001178002.3	c.3701G>C	p.Arg1234Pro	missense_variant	Exon 29 of 29		NP_001171473.1
ATP8B3	NR_047593.3	n.4195G>C		non_coding_transcript_exon_variant	Exon 29 of 29

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP8B3	ENST00000310127.10	c.3812G>C	p.Arg1271Pro	missense_variant	Exon 29 of 29	1	NM_138813.4	ENSP00000311336.6
ATP8B3	ENST00000525591.5	c.3701G>C	p.Arg1234Pro	missense_variant	Exon 29 of 29	1		ENSP00000437115.1
ATP8B3	ENST00000531925.5	n.*3695G>C		non_coding_transcript_exon_variant	Exon 29 of 29	2		ENSP00000444334.1
ATP8B3	ENST00000531925.5	n.*3695G>C		3_prime_UTR_variant	Exon 29 of 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

Feb 12, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.3812G>C (p.R1271P) alteration is located in exon 29 (coding exon 28) of the ATP8B3 gene. This alteration results from a G to C substitution at nucleotide position 3812, causing the arginine (R) at amino acid position 1271 to be replaced by a proline (P). 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	Uncertain	0.38
BayesDel_addAF	Uncertain	0.027	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Uncertain	0.54	D;.
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.36
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.70	T;T
M_CAP	Benign	0.052	D
MetaRNN	Uncertain	0.69	D;D
MetaSVM	Benign	-0.34	T
MutationAssessor	Uncertain	2.8	M;.
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-4.2	D;D
REVEL	Benign	0.27
Sift	Uncertain	0.0010	D;D
Sift4G	Uncertain	0.0030	D;D
Polyphen		1.0	D;.
Vest4		0.53
MutPred		0.55		Loss of MoRF binding (P = 0.0214);.;
MVP		0.70
MPC		0.16
ClinPred		0.98	D
GERP RS		2.4
Varity_R		0.43
gMVP		0.61

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: chr19-1783118;