rs767293026

Variant names:

• chr19-1784848-A-G
• rs767293026
• NM_138813.4:c.3631T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_138813.4(ATP8B3):​c.3631T>C​(p.Phe1211Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000101 in 1,610,086 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000098 (0 hom.)
• Consequence: ATP8B3 NM_138813.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0690
• Publications: 1 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07727608).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138813.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP8B3	NM_138813.4	MANE Select	c.3631T>C	p.Phe1211Leu	missense	Exon 28 of 29	NP_620168.1	O60423-2
	ATP8B3	NM_001178002.3		c.3520T>C	p.Phe1174Leu	missense	Exon 28 of 29	NP_001171473.1	O60423-3
	ATP8B3	NR_047593.3		n.4014T>C		non_coding_transcript_exon	Exon 28 of 29

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP8B3	ENST00000310127.10	TSL:1 MANE Select	c.3631T>C	p.Phe1211Leu	missense	Exon 28 of 29	ENSP00000311336.6	O60423-2
	ATP8B3	ENST00000525591.5	TSL:1	c.3520T>C	p.Phe1174Leu	missense	Exon 28 of 29	ENSP00000437115.1	O60423-3
	ATP8B3	ENST00000531925.5	TSL:2	n.*3514T>C		non_coding_transcript_exon	Exon 28 of 29	ENSP00000444334.1	F5GZM8

Frequencies

GnomAD3 genomes AF: 0.000131 AC: 20 AN: 152198 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000747 AC: 18 AN: 240816 AF XY: 0.0000764

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000236

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000827

Gnomad OTH exome AF: 0.000171

GnomAD4 exome AF: 0.0000981 AC: 143 AN: 1457888 Hom.: 0 Cov.: 30 AF XY: 0.0000883 AC XY: 64 AN XY: 724712

African (AFR) AF: 0.00 AC: 0 AN: 33414

American (AMR) AF: 0.000226 AC: 10 AN: 44252

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26002

East Asian (EAS) AF: 0.00 AC: 0 AN: 39636

South Asian (SAS) AF: 0.00 AC: 0 AN: 85324

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52956

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.000109 AC: 121 AN: 1110274

Other (OTH) AF: 0.000199 AC: 12 AN: 60266

GnomAD4 genome AF: 0.000131 AC: 20 AN: 152198 Hom.: 0 Cov.: 33 AF XY: 0.000148 AC XY: 11 AN XY: 74338

African (AFR) AF: 0.00 AC: 0 AN: 41474

American (AMR) AF: 0.000654 AC: 10 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68016

Other (OTH) AF: 0.000478 AC: 1 AN: 2090

Alfa AF: 0.0000676 Hom.: 0

Bravo AF: 0.000106

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ExAC AF: 0.0000331 AC: 4

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.44
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	0.68
DANN	Benign	0.57
DEOGEN2	Benign	0.10	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.0094	T
MetaRNN	Benign	0.077	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		-0.069
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.15
Sift	Benign	0.62	T
Sift4G	Benign	0.63	T
Polyphen		0.0090	B
Vest4		0.046
MutPred		0.54		Gain of ubiquitination at K1215 (P = 0.1128)
MVP		0.38
MPC		0.089
ClinPred		0.031	T
GERP RS		-2.0
Varity_R		0.094
gMVP		0.50
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs767293026; hg19: chr19-1784847;