rs16963151

Variant names:

• chr15-49987465-T-A
• rs16963151
• NM_024837.4:c.674A>T

Your query was ambiguous. Multiple possible variants found:

• chr15-49987465-T-A
• chr15-49987465-T-C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_024837.4(ATP8B4):​c.674A>T​(p.Asn225Ile) 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 benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ATP8B4 NM_024837.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.184
• Publications: 28 publications found

Genes affected

ATP8B4 (HGNC:13536): (ATPase phospholipid transporting 8B4 (putative)) This gene encodes a member of the cation transport ATPase (P-type) family and type IV subfamily. The encoded protein is involved in phospholipid transport in the cell membrane. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2013]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29128414).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024837.4. 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
	ATP8B4	NM_024837.4	MANE Select	c.674A>T	p.Asn225Ile	missense	Exon 10 of 28	NP_079113.2
	ATP8B4	NR_073596.2		n.915A>T		non_coding_transcript_exon	Exon 11 of 28
	ATP8B4	NR_073597.2		n.827A>T		non_coding_transcript_exon	Exon 10 of 27

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP8B4	ENST00000284509.11	TSL:5 MANE Select	c.674A>T	p.Asn225Ile	missense	Exon 10 of 28	ENSP00000284509.6	Q8TF62
	ATP8B4	ENST00000557955.5	TSL:1	n.674A>T		non_coding_transcript_exon	Exon 10 of 27	ENSP00000453690.1	H0YMP8
	ATP8B4	ENST00000558906.5	TSL:1	n.*393A>T		non_coding_transcript_exon	Exon 11 of 28	ENSP00000452956.1	H0YLJ1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 18148

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.087	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.34	T
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.27
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-0.42	T
MutationAssessor	Benign	1.7	L
PhyloP100		-0.18
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-4.0	D
REVEL	Benign	0.23
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.54	P
Vest4		0.55
MutPred		0.55		Loss of disorder (P = 0.0165)
MVP		0.74
MPC		0.21
ClinPred		0.97	D
GERP RS		-2.2
Varity_R		0.55
gMVP		0.66
Mutation Taster		=88/12	polymorphism

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: rs16963151; hg19: chr15-50279662;