rs7250872

chr19-1811604-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_138813.4(ATP8B3):c.133G>A(p.Gly45Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 1,611,692 control chromosomes in the GnomAD database, including 85,421 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.37 (10864 hom., cov: 33)
  • Exomes 𝑓: 0.31 (74557 hom.)
• Consequence: ATP8B3 NM_138813.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0650

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=3.5777688E-4).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.467 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP8B3	NM_138813.4	c.133G>A	p.Gly45Arg	missense_variant	2/29	ENST00000310127.10
ATP8B3	NM_001178002.3	c.-27G>A		5_prime_UTR_variant	2/29
ATP8B3	NR_047593.3	n.372G>A		non_coding_transcript_exon_variant	2/29

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP8B3	ENST00000310127.10	c.133G>A	p.Gly45Arg	missense_variant	2/29	1	NM_138813.4	A2

Frequencies

GnomAD3 genomes AF: 0.371 AC: 56402 AN: 151990 Hom.: 10855 Cov.: 33

Gnomad AFR AF: 0.473

Gnomad AMI AF: 0.330

Gnomad AMR AF: 0.416

Gnomad ASJ AF: 0.287

Gnomad EAS AF: 0.411

Gnomad SAS AF: 0.324

Gnomad FIN AF: 0.394

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.302

Gnomad OTH AF: 0.343

GnomAD3 exomes AF: 0.347 AC: 85485 AN: 246628 Hom.: 15360 AF XY: 0.339 AC XY: 45554 AN XY: 134438

Gnomad AFR exome AF: 0.480

Gnomad AMR exome AF: 0.423

Gnomad ASJ exome AF: 0.288

Gnomad EAS exome AF: 0.415

Gnomad SAS exome AF: 0.318

Gnomad FIN exome AF: 0.383

Gnomad NFE exome AF: 0.301

Gnomad OTH exome AF: 0.332

GnomAD4 exome AF: 0.315 AC: 459207 AN: 1459584 Hom.: 74557 Cov.: 52 AF XY: 0.314 AC XY: 228144 AN XY: 726094

Gnomad4 AFR exome AF: 0.491

Gnomad4 AMR exome AF: 0.421

Gnomad4 ASJ exome AF: 0.286

Gnomad4 EAS exome AF: 0.455

Gnomad4 SAS exome AF: 0.320

Gnomad4 FIN exome AF: 0.381

Gnomad4 NFE exome AF: 0.297

Gnomad4 OTH exome AF: 0.315

GnomAD4 genome AF: 0.371 AC: 56445 AN: 152108 Hom.: 10864 Cov.: 33 AF XY: 0.374 AC XY: 27830 AN XY: 74360

Gnomad4 AFR AF: 0.473

Gnomad4 AMR AF: 0.416

Gnomad4 ASJ AF: 0.287

Gnomad4 EAS AF: 0.412

Gnomad4 SAS AF: 0.324

Gnomad4 FIN AF: 0.394

Gnomad4 NFE AF: 0.302

Gnomad4 OTH AF: 0.344

Alfa AF: 0.311 Hom.: 14813

Bravo AF: 0.377

TwinsUK AF: 0.290 AC: 1077

ALSPAC AF: 0.297 AC: 1146

ESP6500AA AF: 0.457 AC: 1898

ESP6500EA AF: 0.298 AC: 2506

ExAC AF: 0.344 AC: 41382

Asia WGS AF: 0.352 AC: 1224 AN: 3478

EpiCase AF: 0.290

EpiControl AF: 0.290

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.45
Cadd	Benign	11
Dann	Uncertain	0.99
DEOGEN2	Benign	0.063	T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0020	N
LIST_S2	Benign	0.38	T;T
MetaRNN	Benign	0.00036	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.4	L;.
MutationTaster	Benign	1.0	P;P;P;P
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.94	N;.
REVEL	Benign	0.12
Sift	Pathogenic	0.0	D;.
Sift4G	Uncertain	0.047	D;D
Polyphen		0.013	B;.
Vest4		0.033
MutPred		0.45		Gain of methylation at G45 (P = 0.0221);Gain of methylation at G45 (P = 0.0221);
MPC		0.092
ClinPred		0.011	T
GERP RS		1.4
Varity_R		0.10
gMVP		0.25

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7250872; hg19: chr19-1811603; COSMIC: COSV50074955; COSMIC: COSV50074955;