Variant 4-47512825-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_020453.4(ATP10D):c.285T>A(p.Phe95Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000415 in 1,446,824 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

ATP10D
NM_020453.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.68

Variant links:

Genes affected

ATP10D (HGNC:13549): (ATPase phospholipid transporting 10D (putative)) Enables glycosylceramide flippase activity. Predicted to be involved in phospholipid translocation. Located in endoplasmic reticulum; nucleoplasm; and plasma membrane. Is integral component of plasma membrane. Part of phospholipid-translocating ATPase complex. [provided by Alliance of Genome Resources, Apr 2022]

ATP10D links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.815

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP10D	NM_020453.4 link	c.285T>A	p.Phe95Leu	missense_variant	2/23	ENST00000273859.8	NP_065186.3	Q9P241-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ATP10D	ENST00000273859.8 link	c.285T>A	p.Phe95Leu	missense_variant	2/23	1	NM_020453.4	ENSP00000273859.3	Q9P241-1
ATP10D	ENST00000504445.1 link	c.285T>A	p.Phe95Leu	missense_variant	2/10	1		ENSP00000420909.1	Q6PEW3
ATP10D	ENST00000507889.1 link	n.545T>A		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000405

AC:

AN:

246932

Hom.:

AF XY:

0.00000748

AC XY:

AN XY:

133712

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000896

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000415

AC:

AN:

1446824

Hom.:

Cov.:

AF XY:

0.00000279

AC XY:

AN XY:

717012

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000545

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 04, 2022

The c.285T>A (p.F95L) alteration is located in exon 2 (coding exon 1) of the ATP10D gene. This alteration results from a T to A substitution at nucleotide position 285, causing the phenylalanine (F) at amino acid position 95 to be replaced by a leucine (L). 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

Pathogenic

0.93

BayesDel_addAF

Pathogenic

0.32

BayesDel_noAF

Pathogenic

0.22

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.21

T;.

Eigen

Benign

0.16

Eigen_PC

Benign

0.14

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.95

D;D

M_CAP

Benign

0.061

MetaRNN

Pathogenic

0.82

D;D

MetaSVM

Uncertain

-0.12

MutationAssessor

Uncertain

2.8

M;.

PrimateAI

Pathogenic

0.89

PROVEAN

Uncertain

-4.0

D;D

REVEL

Uncertain

0.61

Sift

Benign

0.17

T;T

Sift4G

Benign

0.064

T;T

Polyphen

0.86

P;B

Vest4

0.90

MutPred

0.69

Loss of helix (P = 0.1706);Loss of helix (P = 0.1706);

MVP

0.67

MPC

0.26

ClinPred

0.74

GERP RS

4.3

Varity_R

0.42

gMVP

0.81

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over