rs3764605

chr19-1784891-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_138813.4(ATP8B3):c.3588T>C(p.Ser1196=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.469 in 1,612,062 control chromosomes in the GnomAD database, including 179,781 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.47 (16906 hom., cov: 33)
  • Exomes 𝑓: 0.47 (162875 hom.)
• Consequence: ATP8B3 NM_138813.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.412

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP7: Synonymous conserved (PhyloP=-0.412 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP8B3	NM_138813.4	c.3588T>C	p.Ser1196=	synonymous_variant	28/29	ENST00000310127.10
ATP8B3	NM_001178002.3	c.3477T>C	p.Ser1159=	synonymous_variant	28/29
ATP8B3	NR_047593.3	n.3971T>C		non_coding_transcript_exon_variant	28/29

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP8B3	ENST00000310127.10	c.3588T>C	p.Ser1196=	synonymous_variant	28/29	1	NM_138813.4	A2
ATP8B3	ENST00000525591.5	c.3477T>C	p.Ser1159=	synonymous_variant	28/29	1		P2
ATP8B3	ENST00000531925.5	c.*3471T>C		3_prime_UTR_variant, NMD_transcript_variant	28/29	2

Frequencies

GnomAD3 genomes AF: 0.467 AC: 71002 AN: 151930 Hom.: 16890 Cov.: 33

Gnomad AFR AF: 0.497

Gnomad AMI AF: 0.501

Gnomad AMR AF: 0.423

Gnomad ASJ AF: 0.510

Gnomad EAS AF: 0.290

Gnomad SAS AF: 0.462

Gnomad FIN AF: 0.397

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.480

Gnomad OTH AF: 0.514

GnomAD3 exomes AF: 0.447 AC: 109827 AN: 245792 Hom.: 25071 AF XY: 0.451 AC XY: 60338 AN XY: 133718

Gnomad AFR exome AF: 0.495

Gnomad AMR exome AF: 0.394

Gnomad ASJ exome AF: 0.503

Gnomad EAS exome AF: 0.282

Gnomad SAS exome AF: 0.468

Gnomad FIN exome AF: 0.404

Gnomad NFE exome AF: 0.479

Gnomad OTH exome AF: 0.474

GnomAD4 exome AF: 0.469 AC: 684840 AN: 1460014 Hom.: 162875 Cov.: 51 AF XY: 0.469 AC XY: 340836 AN XY: 726196

Gnomad4 AFR exome AF: 0.488

Gnomad4 AMR exome AF: 0.398

Gnomad4 ASJ exome AF: 0.508

Gnomad4 EAS exome AF: 0.266

Gnomad4 SAS exome AF: 0.470

Gnomad4 FIN exome AF: 0.410

Gnomad4 NFE exome AF: 0.480

Gnomad4 OTH exome AF: 0.478

GnomAD4 genome AF: 0.467 AC: 71061 AN: 152048 Hom.: 16906 Cov.: 33 AF XY: 0.459 AC XY: 34149 AN XY: 74318

Gnomad4 AFR AF: 0.497

Gnomad4 AMR AF: 0.423

Gnomad4 ASJ AF: 0.510

Gnomad4 EAS AF: 0.290

Gnomad4 SAS AF: 0.463

Gnomad4 FIN AF: 0.397

Gnomad4 NFE AF: 0.480

Gnomad4 OTH AF: 0.509

Alfa AF: 0.483 Hom.: 21229

Bravo AF: 0.469

Asia WGS AF: 0.391 AC: 1363 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.072
Dann	Benign	0.45

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

LitVar

Other links and lift over

dbSNP: rs3764605; hg19: chr19-1784890; COSMIC: COSV59539621; COSMIC: COSV59539621;