Genetic Variant ATP10A:p.Thr1170Thr (chr15-25681057-C-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_024490.4(ATP10A):c.3510G>C(p.Thr1170Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 1,609,916 control chromosomes in the GnomAD database, including 10,511 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.098 ( 896 hom., cov: 33)

Exomes 𝑓: 0.11 ( 9615 hom. )

Consequence

ATP10A
NM_024490.4 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.634

Publications

8 publications found

Variant links:

Genes affected

ATP10A (HGNC:13542): (ATPase phospholipid transporting 10A (putative)) The protein encoded by this gene belongs to the family of P-type cation transport ATPases, and to the subfamily of aminophospholipid-transporting ATPases. The aminophospholipid translocases transport phosphatidylserine and phosphatidylethanolamine from one side of a bilayer to another. This gene is maternally expressed. It maps within the most common interval of deletion responsible for Angelman syndrome, also known as 'happy puppet syndrome'. [provided by RefSeq, Jul 2008]

ATP10A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant 15-25681057-C-G is Benign according to our data. Variant chr15-25681057-C-G is described in ClinVar as Benign. ClinVar VariationId is 3060676.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP10A	NM_024490.4 link	c.3510G>C	p.Thr1170Thr	synonymous_variant	Exon 18 of 21	ENST00000555815.7	NP_077816.1	O60312-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP10A	ENST00000555815.7 link	c.3510G>C	p.Thr1170Thr	synonymous_variant	Exon 18 of 21	5	NM_024490.4	ENSP00000450480.2		O60312-1

Frequencies

GnomAD3 genomes

AF:

0.0980

AC:

14890

AN:

152016

Hom.:

897

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0726

Gnomad AMI

AF:

0.115

Gnomad AMR

AF:

0.0705

Gnomad ASJ

AF:

0.0585

Gnomad EAS

AF:

0.183

Gnomad SAS

AF:

0.255

Gnomad FIN

AF:

0.141

Gnomad MID

AF:

0.155

Gnomad NFE

AF:

0.0969

Gnomad OTH

AF:

0.0904

GnomAD2 exomes

AF:

0.116

AC:

29157

AN:

250822

AF XY:

0.126

show subpopulations

Gnomad AFR exome

AF:

0.0689

Gnomad AMR exome

AF:

0.0480

Gnomad ASJ exome

AF:

0.0592

Gnomad EAS exome

AF:

0.190

Gnomad FIN exome

AF:

0.140

Gnomad NFE exome

AF:

0.0985

Gnomad OTH exome

AF:

0.0974

GnomAD4 exome

AF:

0.105

AC:

153336

AN:

1457780

Hom.:

9615

Cov.:

AF XY:

0.110

AC XY:

80089

AN XY:

725276

show subpopulations

African (AFR)

AF:

0.0683

AC:

2283

AN:

33428

American (AMR)

AF:

0.0516

AC:

2309

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.0585

AC:

1526

AN:

26102

East Asian (EAS)

AF:

0.169

AC:

6721

AN:

39680

South Asian (SAS)

AF:

0.243

AC:

20890

AN:

85902

European-Finnish (FIN)

AF:

0.134

AC:

7174

AN:

53366

Middle Eastern (MID)

AF:

0.141

AC:

810

AN:

5764

European-Non Finnish (NFE)

AF:

0.0947

AC:

104983

AN:

1108580

Other (OTH)

AF:

0.110

AC:

6640

AN:

60248

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

6906

13813

20719

27626

34532

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3930

7860

11790

15720

19650

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0979

AC:

14894

AN:

152136

Hom.:

896

Cov.:

AF XY:

0.103

AC XY:

7681

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.0727

AC:

3019

AN:

41526

American (AMR)

AF:

0.0705

AC:

1078

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0585

AC:

203

AN:

3468

East Asian (EAS)

AF:

0.184

AC:

947

AN:

5156

South Asian (SAS)

AF:

0.255

AC:

1225

AN:

4810

European-Finnish (FIN)

AF:

0.141

AC:

1495

AN:

10570

Middle Eastern (MID)

AF:

0.136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0970

AC:

6593

AN:

68000

Other (OTH)

AF:

0.0895

AC:

189

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

716

1432

2147

2863

3579

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

182

364

546

728

910

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0590

Hom.:

Bravo

AF:

0.0881

Asia WGS

AF:

0.192

AC:

668

AN:

3478

EpiCase

AF:

0.0965

EpiControl

AF:

0.101

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ATP10A-related disorder

Benign:1

Nov 15, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

0.045

(source)

DANN

Benign

0.54

PhyloP100

-0.63

Mutation Taster

=98/2

polymorphism (auto)

(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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over