5-160565589-G-A

Variant names:

• chr5-160565589-G-A
• rs763110476
• NM_025153.3:c.4250C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_025153.3(ATP10B):​c.4250C>T​(p.Ser1417Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,818 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: ATP10B NM_025153.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.990
• Publications: 0 publications found

Genes affected

ATP10B (HGNC:13543): (ATPase phospholipid transporting 10B (putative)) Enables glycosylceramide flippase activity and phosphatidylcholine flippase activity. Involved in lysosomal membrane organization. Located in endoplasmic reticulum. Is integral component of lysosomal membrane. Part of phospholipid-translocating ATPase complex. [provided by Alliance of Genome Resources, Apr 2022]

MIR3142HG (HGNC:51944): (MIR3142 host gene)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07705197).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025153.3. 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
	ATP10B	NM_025153.3	MANE Select	c.4250C>T	p.Ser1417Phe	missense	Exon 26 of 26	NP_079429.2	O94823-1
	ATP10B	NM_001366652.1		c.4250C>T	p.Ser1417Phe	missense	Exon 25 of 25	NP_001353581.1	O94823-1
	ATP10B	NM_001366655.1		c.4250C>T	p.Ser1417Phe	missense	Exon 25 of 25	NP_001353584.1	O94823-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP10B	ENST00000327245.10	TSL:1 MANE Select	c.4250C>T	p.Ser1417Phe	missense	Exon 26 of 26	ENSP00000313600.5	O94823-1
	ATP10B	ENST00000943128.1		c.4250C>T	p.Ser1417Phe	missense	Exon 26 of 26	ENSP00000613187.1
	ATP10B	ENST00000642502.1		c.4166C>T	p.Ser1389Phe	missense	Exon 21 of 21	ENSP00000493802.1	A0A2R8YDI5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000803 AC: 2 AN: 249062 AF XY: 0.00000740

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000579

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461818 Hom.: 0 Cov.: 29 AF XY: 0.00000138 AC XY: 1 AN XY: 727210

African (AFR) AF: 0.0000299 AC: 1 AN: 33476

American (AMR) AF: 0.0000447 AC: 2 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111956

Other (OTH) AF: 0.0000166 AC: 1 AN: 60396

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.00000826 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	13
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0079	T
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.064	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.077	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L
PhyloP100		0.99
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.029
Sift	Benign	0.047	D
Sift4G	Uncertain	0.0060	D
Polyphen		0.0	B
Vest4		0.12
MutPred		0.25		Loss of phosphorylation at S1417 (P = 0.0205)
MVP		0.50
MPC		0.086
ClinPred		0.12	T
GERP RS		0.38
Varity_R		0.040
gMVP		0.27
Mutation Taster		=92/8	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: rs763110476; hg19: chr5-159992596;