5-160565493-C-T

Variant names:

• chr5-160565493-C-T
• rs201409494
• NM_025153.3:c.4346G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_025153.3(ATP10B):​c.4346G>A​(p.Arg1449Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000723 in 1,614,106 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00038 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00076 (1 hom.)
• Consequence: ATP10B NM_025153.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.296
• Publications: 4 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.024545997).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP10B	NM_025153.3	c.4346G>A	p.Arg1449Lys	missense_variant	Exon 26 of 26	ENST00000327245.10	NP_079429.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP10B	ENST00000327245.10	c.4346G>A	p.Arg1449Lys	missense_variant	Exon 26 of 26	1	NM_025153.3	ENSP00000313600.5

Frequencies

GnomAD3 genomes AF: 0.000381 AC: 58 AN: 152198 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000750

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000185 AC: 46 AN: 248928 AF XY: 0.000193

Gnomad AFR exome AF: 0.000129

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000557

Gnomad FIN exome AF: 0.000186

Gnomad NFE exome AF: 0.000319

Gnomad OTH exome AF: 0.000331

GnomAD4 exome AF: 0.000759 AC: 1109 AN: 1461790 Hom.: 1 Cov.: 29 AF XY: 0.000736 AC XY: 535 AN XY: 727198

African (AFR) AF: 0.0000896 AC: 3 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: 0.0000252 AC: 1 AN: 39690

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

European-Finnish (FIN) AF: 0.000225 AC: 12 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.000958 AC: 1065 AN: 1111936

Other (OTH) AF: 0.000431 AC: 26 AN: 60390

GnomAD4 genome AF: 0.000381 AC: 58 AN: 152316 Hom.: 0 Cov.: 32 AF XY: 0.000322 AC XY: 24 AN XY: 74484

African (AFR) AF: 0.000168 AC: 7 AN: 41574

American (AMR) AF: 0.00 AC: 0 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000750 AC: 51 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000488 Hom.: 0

Bravo AF: 0.000298

TwinsUK AF: 0.00108 AC: 4

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000356 AC: 3

ExAC AF: 0.000165 AC: 20

EpiCase AF: 0.000654

EpiControl AF: 0.000534

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 23, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.4346G>A (p.R1449K) alteration is located in exon 26 (coding exon 22) of the ATP10B gene. This alteration results from a G to A substitution at nucleotide position 4346, causing the arginine (R) at amino acid position 1449 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	6.6
DANN	Benign	0.88
DEOGEN2	Benign	0.0021	.;T
Eigen	Benign	-0.99
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.26	T;T
M_CAP	Benign	0.0068	T
MetaRNN	Benign	0.025	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.63	.;N
PhyloP100		-0.30
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.15	.;N
REVEL	Benign	0.026
Sift	Benign	0.57	.;T
Sift4G	Benign	0.52	.;T
Polyphen		0.0	.;B
Vest4		0.048
MVP		0.32
MPC		0.078
ClinPred		0.011	T
GERP RS		-0.73
Varity_R		0.038
gMVP		0.084
Mutation Taster		=97/3	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: rs201409494; hg19: chr5-159992500;