Genetic Variant NM_025153.3:c.4198G>C (chr5-160565641-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_025153.3(ATP10B):c.4198G>C(p.Glu1400Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,814 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E1400K) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

ATP10B
NM_025153.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.157

Publications

1 publications found

Variant links:

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]

ATP10B links:

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

MIR3142HG links:

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ACMG classification

Classification was made for transcript

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=0.07255766).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP10B	NM_025153.3 link	c.4198G>C	p.Glu1400Gln	missense_variant	Exon 26 of 26	ENST00000327245.10	NP_079429.2	O94823-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP10B	ENST00000327245.10 link	c.4198G>C	p.Glu1400Gln	missense_variant	Exon 26 of 26	1	NM_025153.3	ENSP00000313600.5		O94823-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000803

AC:

AN:

249106

AF XY:

0.0000148

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000410

AC:

AN:

1461814

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727210

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39686

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00000360

AC:

AN:

1111960

Other (OTH)

AF:

0.0000166

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.63

(source)

DANN

Benign

0.37

DEOGEN2

Benign

0.0018

.;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.98

FATHMM_MKL

Benign

0.088

LIST_S2

Benign

0.37

T;T

M_CAP

Benign

0.0059

MetaRNN

Benign

0.073

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

.;N

PhyloP100

0.16

PrimateAI

Benign

0.21

PROVEAN

Benign

-0.15

.;N

REVEL

Benign

0.051

Sift

Benign

0.58

.;T

Sift4G

Benign

0.59

.;T

Polyphen

0.20

.;B

Vest4

0.034

MutPred

0.21

.;Gain of sheet (P = 0.1208);

MVP

0.36

MPC

0.097

ClinPred

0.038

GERP RS

3.3

Varity_R

0.050

gMVP

0.23

Mutation Taster

=97/3

polymorphism

(source)

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

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NM_025153.3:c.4198G>C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over