rs34315917

Variant names:

• chr18-57691850-T-A
• rs34315917
• NM_001374385.1:c.1177A>T

Your query was ambiguous. Multiple possible variants found:

• chr18-57691850-T-A
• chr18-57691850-T-C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001374385.1(ATP8B1):​c.1177A>T​(p.Ile393Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. I393V) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ATP8B1 NM_001374385.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.85
• Publications: 0 publications found

Genes affected

ATP8B1 (HGNC:3706): (ATPase phospholipid transporting 8B1) This gene encodes a member of the P-type cation transport ATPase family, which belongs to the subfamily of aminophospholipid-transporting ATPases. The aminophospholipid translocases transport phosphatidylserine and phosphatidylethanolamine from one side of a bilayer to another. Mutations in this gene may result in progressive familial intrahepatic cholestasis type 1 and in benign recurrent intrahepatic cholestasis. [provided by RefSeq, Jul 2008]

ATP8B1-AS1 (HGNC:56042): (ATP8B1 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.795

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP8B1	NM_001374385.1	c.1177A>T	p.Ile393Phe	missense_variant	Exon 12 of 28	ENST00000648908.2	NP_001361314.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP8B1	ENST00000648908.2	c.1177A>T	p.Ile393Phe	missense_variant	Exon 12 of 28		NM_001374385.1	ENSP00000497896.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.44
BayesDel_addAF	Pathogenic	0.39	D
BayesDel_noAF	Pathogenic	0.33
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.54	D;D
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.86	.;D
M_CAP	Uncertain	0.092	D
MetaRNN	Pathogenic	0.79	D;D
MetaSVM	Uncertain	0.66	D
MutationAssessor	Benign	1.5	L;L
PhyloP100		2.9
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-1.9	N;.
REVEL	Pathogenic	0.69
Sift	Benign	0.16	T;.
Sift4G	Benign	0.12	T;.
Polyphen		0.99	D;D
Vest4		0.70
MutPred		0.44		Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);
MVP		0.96
ClinPred		0.82	D
GERP RS		6.1
Varity_R		0.27
gMVP		0.91
Mutation Taster		=12/88	disease causing

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: rs34315917; hg19: chr18-55359082;