rs3764605

Variant names:

• chr19-1784891-A-G
• rs3764605
• NM_138813.4:c.3588T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_138813.4(ATP8B3):​c.3588T>C​(p.Ser1196Ser) 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
• Publications: 14 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 -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 rank	MANE	Protein	UniProt
ATP8B3	NM_138813.4	c.3588T>C	p.Ser1196Ser	synonymous_variant	Exon 28 of 29	ENST00000310127.10	NP_620168.1
ATP8B3	NM_001178002.3	c.3477T>C	p.Ser1159Ser	synonymous_variant	Exon 28 of 29		NP_001171473.1
ATP8B3	NR_047593.3	n.3971T>C		non_coding_transcript_exon_variant	Exon 28 of 29

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP8B3	ENST00000310127.10	c.3588T>C	p.Ser1196Ser	synonymous_variant	Exon 28 of 29	1	NM_138813.4	ENSP00000311336.6
ATP8B3	ENST00000525591.5	c.3477T>C	p.Ser1159Ser	synonymous_variant	Exon 28 of 29	1		ENSP00000437115.1
ATP8B3	ENST00000531925.5	n.*3471T>C		non_coding_transcript_exon_variant	Exon 28 of 29	2		ENSP00000444334.1
ATP8B3	ENST00000531925.5	n.*3471T>C		3_prime_UTR_variant	Exon 28 of 29	2		ENSP00000444334.1

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

GnomAD2 exomes AF: 0.447 AC: 109827 AN: 245792 AF XY: 0.451

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 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

African (AFR) AF: 0.488 AC: 16325 AN: 33468

American (AMR) AF: 0.398 AC: 17719 AN: 44530

Ashkenazi Jewish (ASJ) AF: 0.508 AC: 13229 AN: 26052

East Asian (EAS) AF: 0.266 AC: 10542 AN: 39656

South Asian (SAS) AF: 0.470 AC: 40408 AN: 86030

European-Finnish (FIN) AF: 0.410 AC: 21732 AN: 53000

Middle Eastern (MID) AF: 0.503 AC: 2893 AN: 5756

European-Non Finnish (NFE) AF: 0.480 AC: 533136 AN: 1111194

Other (OTH) AF: 0.478 AC: 28856 AN: 60328

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

African (AFR) AF: 0.497 AC: 20623 AN: 41496

American (AMR) AF: 0.423 AC: 6461 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.510 AC: 1765 AN: 3464

East Asian (EAS) AF: 0.290 AC: 1499 AN: 5168

South Asian (SAS) AF: 0.463 AC: 2232 AN: 4816

European-Finnish (FIN) AF: 0.397 AC: 4191 AN: 10556

Middle Eastern (MID) AF: 0.578 AC: 170 AN: 294

European-Non Finnish (NFE) AF: 0.480 AC: 32588 AN: 67950

Other (OTH) AF: 0.509 AC: 1075 AN: 2110

Alfa AF: 0.484 Hom.: 26782

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
PhyloP100		-0.41
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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