19-1784920-G-C

Variant names:

• chr19-1784920-G-C
• NM_138813.4:c.3559C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_138813.4(ATP8B3):​c.3559C>G​(p.Pro1187Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,460,504 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P1187S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ATP8B3 NM_138813.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.94

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22523648).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP8B3	NM_138813.4	c.3559C>G	p.Pro1187Ala	missense_variant	Exon 28 of 29	ENST00000310127.10	NP_620168.1
ATP8B3	NM_001178002.3	c.3448C>G	p.Pro1150Ala	missense_variant	Exon 28 of 29		NP_001171473.1
ATP8B3	NR_047593.3	n.3942C>G		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.3559C>G	p.Pro1187Ala	missense_variant	Exon 28 of 29	1	NM_138813.4	ENSP00000311336.6
ATP8B3	ENST00000525591.5	c.3448C>G	p.Pro1150Ala	missense_variant	Exon 28 of 29	1		ENSP00000437115.1
ATP8B3	ENST00000531925.5	n.*3442C>G		non_coding_transcript_exon_variant	Exon 28 of 29	2		ENSP00000444334.1
ATP8B3	ENST00000531925.5	n.*3442C>G		3_prime_UTR_variant	Exon 28 of 29	2		ENSP00000444334.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460504 Hom.: 0 Cov.: 54 AF XY: 0.00000138 AC XY: 1 AN XY: 726438

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	17
DANN	Benign	0.94
DEOGEN2	Benign	0.26	T;.
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.47
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.46	T;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.23	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L;.
PrimateAI	Benign	0.32	T
PROVEAN	Pathogenic	-5.7	D;D
REVEL	Benign	0.10
Sift	Benign	0.11	T;T
Sift4G	Benign	0.22	T;T
Polyphen		0.13	B;.
Vest4		0.17
MutPred		0.38		Gain of catalytic residue at P1187 (P = 0.0394);.;
MVP		0.49
MPC		0.20
ClinPred		0.77	D
GERP RS		2.5
Varity_R		0.19
gMVP		0.36

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-1784919;