Variant 4-47535529-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The ENST00000273859.8(ATP10D):c.797G>A(p.Arg266His) variant causes a missense change. The variant allele was found at a frequency of 0.0004 in 1,612,052 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00042 ( 3 hom. )

Consequence

ATP10D
ENST00000273859.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.85

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.23244652).

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP10D	NM_020453.4 linkuse as main transcript	c.797G>A	p.Arg266His	missense_variant	6/23	ENST00000273859.8	NP_065186.3	Q9P241-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP10D	ENST00000273859.8 linkuse as main transcript	c.797G>A	p.Arg266His	missense_variant	6/23	1	NM_020453.4	ENSP00000273859.3		Q9P241-1
ATP10D	ENST00000504445.1 linkuse as main transcript	c.797G>A	p.Arg266His	missense_variant	6/10	1		ENSP00000420909.1		Q6PEW3

Frequencies

GnomAD3 genomes

AF:

0.000217

AC:

AN:

152016

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000328

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000309

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000352

AC:

AN:

249898

Hom.:

AF XY:

0.000452

AC XY:

AN XY:

135030

show subpopulations

Gnomad AFR exome

AF:

0.0000618

Gnomad AMR exome

AF:

0.000233

Gnomad ASJ exome

AF:

0.000899

Gnomad EAS exome

AF:

0.000164

Gnomad SAS exome

AF:

0.000330

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000477

Gnomad OTH exome

AF:

0.000491

GnomAD4 exome

AF:

0.000419

AC:

612

AN:

1459918

Hom.:

Cov.:

AF XY:

0.000454

AC XY:

330

AN XY:

726200

show subpopulations

Gnomad4 AFR exome

AF:

0.000420

Gnomad4 AMR exome

AF:

0.000338

Gnomad4 ASJ exome

AF:

0.00104

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.000454

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000411

Gnomad4 OTH exome

AF:

0.000547

GnomAD4 genome

AF:

0.000217

AC:

AN:

152134

Hom.:

Cov.:

AF XY:

0.000202

AC XY:

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000328

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000309

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000443

Hom.:

Bravo

AF:

0.000298

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.000288

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000546

EpiControl

AF:

0.000593

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

Apr 25, 2022

The c.797G>A (p.R266H) alteration is located in exon 6 (coding exon 5) of the ATP10D gene. This alteration results from a G to A substitution at nucleotide position 797, causing the arginine (R) at amino acid position 266 to be replaced by a histidine (H). 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

0.15

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.11

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.44

T;.

Eigen

Uncertain

0.62

Eigen_PC

Uncertain

0.62

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.63

T;T

M_CAP

Benign

0.030

MetaRNN

Benign

0.23

T;T

MetaSVM

Uncertain

0.061

MutationAssessor

Uncertain

2.2

M;.

MutationTaster

Benign

0.97

D;D

PrimateAI

Benign

0.43

PROVEAN

Uncertain

-3.7

D;D

REVEL

Uncertain

0.42

Sift

Uncertain

0.0070

D;D

Sift4G

Uncertain

0.0030

D;D

Polyphen

0.96

D;D

Vest4

0.35

MVP

0.90

MPC

0.67

ClinPred

0.13

GERP RS

5.7

Varity_R

0.42

gMVP

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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