5-160589677-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_025153.3(ATP10B):c.3665T>C(p.Ile1222Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0108 in 1,613,798 control chromosomes in the GnomAD database, including 152 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (16 hom., cov: 32)
  • Exomes 𝑓: 0.011 (136 hom.)
• Consequence: ATP10B NM_025153.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 7.39

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005785674).
• BP6: Variant 5-160589677-A-G is Benign according to our data. Variant chr5-160589677-A-G is described in ClinVar as [Benign]. Clinvar id is 3024776.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.0108 (15711/1461488) while in subpopulation MID AF= 0.025 (144/5768). AF 95% confidence interval is 0.0216. There are 136 homozygotes in gnomad4_exome. There are 7924 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP10B	NM_025153.3	c.3665T>C	p.Ile1222Thr	missense_variant	24/26	ENST00000327245.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP10B	ENST00000327245.10	c.3665T>C	p.Ile1222Thr	missense_variant	24/26	1	NM_025153.3	P1
ATP10B	ENST00000642502.1	c.3581T>C	p.Ile1194Thr	missense_variant	19/21

Frequencies

GnomAD3 genomes AF: 0.0114 AC: 1728 AN: 152192 Hom.: 16 Cov.: 32

Gnomad AFR AF: 0.00714

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00942

Gnomad ASJ AF: 0.0118

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.0178

Gnomad FIN AF: 0.0433

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.00973

Gnomad OTH AF: 0.0110

GnomAD3 exomes AF: 0.0130 AC: 3245 AN: 249244 Hom.: 42 AF XY: 0.0136 AC XY: 1834 AN XY: 135206

Gnomad AFR exome AF: 0.00659

Gnomad AMR exome AF: 0.00890

Gnomad ASJ exome AF: 0.0107

Gnomad EAS exome AF: 0.000780

Gnomad SAS exome AF: 0.0156

Gnomad FIN exome AF: 0.0380

Gnomad NFE exome AF: 0.0119

Gnomad OTH exome AF: 0.0114

GnomAD4 exome AF: 0.0107 AC: 15711 AN: 1461488 Hom.: 136 Cov.: 30 AF XY: 0.0109 AC XY: 7924 AN XY: 727074

Gnomad4 AFR exome AF: 0.00595

Gnomad4 AMR exome AF: 0.00886

Gnomad4 ASJ exome AF: 0.0107

Gnomad4 EAS exome AF: 0.000428

Gnomad4 SAS exome AF: 0.0153

Gnomad4 FIN exome AF: 0.0348

Gnomad4 NFE exome AF: 0.00980

Gnomad4 OTH exome AF: 0.0101

GnomAD4 genome AF: 0.0114 AC: 1729 AN: 152310 Hom.: 16 Cov.: 32 AF XY: 0.0132 AC XY: 980 AN XY: 74474

Gnomad4 AFR AF: 0.00714

Gnomad4 AMR AF: 0.00948

Gnomad4 ASJ AF: 0.0118

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0178

Gnomad4 FIN AF: 0.0433

Gnomad4 NFE AF: 0.00973

Gnomad4 OTH AF: 0.0109

Alfa AF: 0.00994 Hom.: 10

Bravo AF: 0.00791

TwinsUK AF: 0.00998 AC: 37

ALSPAC AF: 0.00752 AC: 29

ESP6500AA AF: 0.00666 AC: 26

ESP6500EA AF: 0.0108 AC: 89

ExAC AF: 0.0133 AC: 1608

Asia WGS AF: 0.0140 AC: 48 AN: 3476

EpiCase AF: 0.0102

EpiControl AF: 0.0111

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2024

ATP10B: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.38
Cadd	Uncertain	24
Dann	Uncertain	0.98
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.83	T;T
MetaRNN	Benign	0.0058	T;T
MetaSVM	Benign	-0.92	T
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.50	T
Polyphen		1.0	.;D
Vest4		0.19
MPC		0.15
ClinPred		0.036	T
GERP RS		5.4
Varity_R		0.23
gMVP		0.64

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

LitVar

Other links and lift over

dbSNP: rs144497343; hg19: chr5-160016684; COSMIC: COSV59160698;