19-1783237-TCTC-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PM4_Supporting BP6_Moderate BS2

The NM_138813.4(ATP8B3):c.3691_3693del(p.Glu1231del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00355 in 1,610,048 control chromosomes in the GnomAD database, including 21 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0031 (1 hom., cov: 31)
  • Exomes 𝑓: 0.0036 (20 hom.)
• Consequence: ATP8B3 NM_138813.4 inframe_deletion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0900

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 Likely_benign. Variant got -5 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_138813.4. Strenght limited to Supporting due to length of the change: 1aa.
• BP6: Variant 19-1783237-TCTC-T is Benign according to our data. Variant chr19-1783237-TCTC-T is described in ClinVar as [Likely_benign]. Clinvar id is 716789.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP8B3	NM_138813.4	c.3691_3693del	p.Glu1231del	inframe_deletion	29/29	ENST00000310127.10
ATP8B3	NM_001178002.3	c.3580_3582del	p.Glu1194del	inframe_deletion	29/29
ATP8B3	NR_047593.3	n.4074_4076del		non_coding_transcript_exon_variant	29/29

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP8B3	ENST00000310127.10	c.3691_3693del	p.Glu1231del	inframe_deletion	29/29	1	NM_138813.4	A2
ATP8B3	ENST00000525591.5	c.3580_3582del	p.Glu1194del	inframe_deletion	29/29	1		P2
ATP8B3	ENST00000531925.5	c.*3574_*3576del		3_prime_UTR_variant, NMD_transcript_variant	29/29	2

Frequencies

GnomAD3 genomes AF: 0.00308 AC: 465 AN: 151092 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.000925

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.000725

Gnomad ASJ AF: 0.00260

Gnomad EAS AF: 0.000195

Gnomad SAS AF: 0.00316

Gnomad FIN AF: 0.00134

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00543

Gnomad OTH AF: 0.00194

GnomAD3 exomes AF: 0.00286 AC: 695 AN: 243066 Hom.: 5 AF XY: 0.00307 AC XY: 406 AN XY: 132262

Gnomad AFR exome AF: 0.000670

Gnomad AMR exome AF: 0.000945

Gnomad ASJ exome AF: 0.00142

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00258

Gnomad FIN exome AF: 0.00198

Gnomad NFE exome AF: 0.00459

Gnomad OTH exome AF: 0.00286

GnomAD4 exome AF: 0.00360 AC: 5247 AN: 1458838 Hom.: 20 AF XY: 0.00344 AC XY: 2496 AN XY: 725480

Gnomad4 AFR exome AF: 0.000508

Gnomad4 AMR exome AF: 0.000836

Gnomad4 ASJ exome AF: 0.00177

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00266

Gnomad4 FIN exome AF: 0.00242

Gnomad4 NFE exome AF: 0.00416

Gnomad4 OTH exome AF: 0.00279

GnomAD4 genome AF: 0.00308 AC: 466 AN: 151210 Hom.: 1 Cov.: 31 AF XY: 0.00267 AC XY: 197 AN XY: 73838

Gnomad4 AFR AF: 0.000923

Gnomad4 AMR AF: 0.000724

Gnomad4 ASJ AF: 0.00260

Gnomad4 EAS AF: 0.000196

Gnomad4 SAS AF: 0.00337

Gnomad4 FIN AF: 0.00134

Gnomad4 NFE AF: 0.00543

Gnomad4 OTH AF: 0.00192

Alfa AF: 0.00330 Hom.: 0

Bravo AF: 0.00274

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Mar 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs530525816; hg19: chr19-1783236;