rs7250872

Variant names:

• chr19-1811604-C-T
• rs7250872
• NM_138813.4:c.133G>A

Variant summary

Our verdict is Benign. The variant received -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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 51 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: Benign. The variant received -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.

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.133G>A	p.Gly45Arg	missense	Exon 2 of 29	NP_620168.1
	ATP8B3	NM_001178002.3		c.-27G>A		5_prime_UTR	Exon 2 of 29	NP_001171473.1
	ATP8B3	NR_047593.3		n.372G>A		non_coding_transcript_exon	Exon 2 of 29

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP8B3	ENST00000310127.10	TSL:1 MANE Select	c.133G>A	p.Gly45Arg	missense	Exon 2 of 29	ENSP00000311336.6
	ATP8B3	ENST00000525591.5	TSL:1	c.-27G>A		5_prime_UTR	Exon 2 of 29	ENSP00000437115.1
	ATP8B3	ENST00000587160.2	TSL:5	c.133G>A	p.Gly45Arg	missense	Exon 2 of 6	ENSP00000465027.2

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

GnomAD2 exomes AF: 0.347 AC: 85485 AN: 246628 AF XY: 0.339

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 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

African (AFR) AF: 0.491 AC: 16422 AN: 33472

American (AMR) AF: 0.421 AC: 18807 AN: 44646

Ashkenazi Jewish (ASJ) AF: 0.286 AC: 7482 AN: 26128

East Asian (EAS) AF: 0.455 AC: 18051 AN: 39678

South Asian (SAS) AF: 0.320 AC: 27567 AN: 86230

European-Finnish (FIN) AF: 0.381 AC: 19674 AN: 51644

Middle Eastern (MID) AF: 0.297 AC: 1715 AN: 5768

European-Non Finnish (NFE) AF: 0.297 AC: 330450 AN: 1111672

Other (OTH) AF: 0.315 AC: 19039 AN: 60346

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

African (AFR) AF: 0.473 AC: 19608 AN: 41494

American (AMR) AF: 0.416 AC: 6357 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.287 AC: 994 AN: 3468

East Asian (EAS) AF: 0.412 AC: 2126 AN: 5154

South Asian (SAS) AF: 0.324 AC: 1565 AN: 4824

European-Finnish (FIN) AF: 0.394 AC: 4168 AN: 10590

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.302 AC: 20515 AN: 67968

Other (OTH) AF: 0.344 AC: 726 AN: 2110

Alfa AF: 0.320 Hom.: 32359

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 v4.9

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
MetaRNN	Benign	0.00036	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.4	L
PhyloP100		-0.065
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.94	N
REVEL	Benign	0.12
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.047	D
Polyphen		0.013	B
Vest4		0.033
MutPred		0.45		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
Mutation Taster		=298/2	polymorphism (auto)

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

Other links and lift over

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