NM_025153.3:c.-331+16475T>A

Variant names:

• chr5-160769084-A-T
• rs4476766
• NM_025153.3:c.-331+16475T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_025153.3(ATP10B):​c.-331+16475T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 152,126 control chromosomes in the GnomAD database, including 3,655 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 0.20 (3655 hom., cov: 32)
• Consequence: ATP10B NM_025153.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.415
• Publications: 2 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.495 is higher than 0.05.

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.-331+16475T>A		intron	N/A	NP_079429.2
	ATP10B	NM_001366652.1		c.-147+16652T>A		intron	N/A	NP_001353581.1
	ATP10B	NM_001366655.1		c.-147+16475T>A		intron	N/A	NP_001353584.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP10B	ENST00000327245.10	TSL:1 MANE Select	c.-331+16475T>A		intron	N/A	ENSP00000313600.5
	ATP10B	ENST00000943128.1		c.-147+14757T>A		intron	N/A	ENSP00000613187.1
	ATP10B	ENST00000517802.5	TSL:2	n.517+16475T>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30386 AN: 152006 Hom.: 3641 Cov.: 32

Gnomad AFR AF: 0.229

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.511

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.209

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.200 AC: 30433 AN: 152126 Hom.: 3655 Cov.: 32 AF XY: 0.208 AC XY: 15443 AN XY: 74368

African (AFR) AF: 0.229 AC: 9512 AN: 41482

American (AMR) AF: 0.308 AC: 4706 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 548 AN: 3470

East Asian (EAS) AF: 0.511 AC: 2636 AN: 5160

South Asian (SAS) AF: 0.263 AC: 1267 AN: 4826

European-Finnish (FIN) AF: 0.141 AC: 1498 AN: 10592

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.142 AC: 9659 AN: 68004

Other (OTH) AF: 0.217 AC: 458 AN: 2110

Alfa AF: 0.166 Hom.: 272

Bravo AF: 0.218

Asia WGS AF: 0.381 AC: 1323 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.5
DANN	Benign	0.74
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: rs4476766; hg19: chr5-160196091;