Variant 4-47536467-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020453.4(ATP10D):c.1046A>G(p.Lys349Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000719 in 1,613,524 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000075 ( 0 hom. )

Consequence

ATP10D
NM_020453.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.89

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06988123).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP10D	NM_020453.4 linkuse as main transcript	c.1046A>G	p.Lys349Arg	missense_variant	8/23	ENST00000273859.8	NP_065186.3	Q9P241-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ATP10D	ENST00000273859.8 linkuse as main transcript	c.1046A>G	p.Lys349Arg	missense_variant	8/23	1	NM_020453.4	ENSP00000273859.3	Q9P241-1
ATP10D	ENST00000504445.1 linkuse as main transcript	c.1046A>G	p.Lys349Arg	missense_variant	8/10	1		ENSP00000420909.1	Q6PEW3
ATP10D	ENST00000503288.6 linkuse as main transcript	n.-14A>G		upstream_gene_variant		2		ENSP00000421536.1	H0Y8M7

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000598

AC:

AN:

250726

Hom.:

AF XY:

0.0000664

AC XY:

AN XY:

135500

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.000203

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:

0.0000619

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000753

AC:

110

AN:

1461406

Hom.:

Cov.:

AF XY:

0.0000674

AC XY:

AN XY:

727024

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000291

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:

0.0000828

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152118

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000847

Hom.:

Bravo

AF:

0.0000340

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.0000906

AC:

EpiCase

AF:

0.0000546

EpiControl

AF:

0.000296

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

Oct 06, 2021

The c.1046A>G (p.K349R) alteration is located in exon 8 (coding exon 7) of the ATP10D gene. This alteration results from a A to G substitution at nucleotide position 1046, causing the lysine (K) at amino acid position 349 to be replaced by an arginine (R). 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

0.072

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Benign

0.81

DEOGEN2

Benign

0.14

T;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.38

LIST_S2

Benign

0.72

T;T

M_CAP

Benign

0.051

MetaRNN

Benign

0.070

T;T

MetaSVM

Benign

-0.72

MutationAssessor

Benign

1.2

L;.

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.85

N;N

REVEL

Benign

0.12

Sift

Benign

0.23

T;T

Sift4G

Benign

0.40

T;T

Polyphen

0.0020

B;B

Vest4

0.21

MutPred

0.39

Loss of ubiquitination at K349 (P = 0.0118);Loss of ubiquitination at K349 (P = 0.0118);

MVP

0.71

MPC

0.14

ClinPred

0.027

GERP RS

3.2

Varity_R

0.035

gMVP

0.48

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