19-1783237-TCTC-T

Variant names:

• chr19-1783237-TCTC-T
• rs530525816
• NM_138813.4:c.3691_3693delGAG

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 1P and 6B. PM4_Supporting BP6_Moderate BS2

The NM_138813.4(ATP8B3):​c.3691_3693delGAG​(p.Glu1231del) variant causes a conservative 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 conservative_inframe_deletion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0900
• Publications: 0 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 -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 VariationId is 716789.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 20 AR gene

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.3691_3693delGAG	p.Glu1231del	conservative_inframe_deletion	Exon 29 of 29	NP_620168.1	O60423-2
	ATP8B3	NM_001178002.3		c.3580_3582delGAG	p.Glu1194del	conservative_inframe_deletion	Exon 29 of 29	NP_001171473.1	O60423-3
	ATP8B3	NR_047593.3		n.4074_4076delGAG		non_coding_transcript_exon	Exon 29 of 29

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP8B3	ENST00000310127.10	TSL:1 MANE Select	c.3691_3693delGAG	p.Glu1231del	conservative_inframe_deletion	Exon 29 of 29	ENSP00000311336.6	O60423-2
	ATP8B3	ENST00000525591.5	TSL:1	c.3580_3582delGAG	p.Glu1194del	conservative_inframe_deletion	Exon 29 of 29	ENSP00000437115.1	O60423-3
	ATP8B3	ENST00000531925.5	TSL:2	n.*3574_*3576delGAG		non_coding_transcript_exon	Exon 29 of 29	ENSP00000444334.1	F5GZM8

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

GnomAD2 exomes AF: 0.00286 AC: 695 AN: 243066 AF XY: 0.00307

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 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

African (AFR) AF: 0.000508 AC: 17 AN: 33452

American (AMR) AF: 0.000836 AC: 37 AN: 44264

Ashkenazi Jewish (ASJ) AF: 0.00177 AC: 46 AN: 26046

East Asian (EAS) AF: 0.00 AC: 0 AN: 39644

South Asian (SAS) AF: 0.00266 AC: 228 AN: 85714

European-Finnish (FIN) AF: 0.00242 AC: 128 AN: 52992

Middle Eastern (MID) AF: 0.000867 AC: 5 AN: 5766

European-Non Finnish (NFE) AF: 0.00416 AC: 4618 AN: 1110652

Other (OTH) AF: 0.00279 AC: 168 AN: 60308

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

African (AFR) AF: 0.000923 AC: 38 AN: 41182

American (AMR) AF: 0.000724 AC: 11 AN: 15194

Ashkenazi Jewish (ASJ) AF: 0.00260 AC: 9 AN: 3464

East Asian (EAS) AF: 0.000196 AC: 1 AN: 5112

South Asian (SAS) AF: 0.00337 AC: 16 AN: 4750

European-Finnish (FIN) AF: 0.00134 AC: 14 AN: 10448

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00543 AC: 368 AN: 67774

Other (OTH) AF: 0.00192 AC: 4 AN: 2082

Alfa AF: 0.00330 Hom.: 0

Bravo AF: 0.00274

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.090
Mutation Taster		=77/23	polymorphism

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

Other links and lift over

dbSNP: rs530525816; hg19: chr19-1783236; COSMIC: COSV59545863; COSMIC: COSV59545863;