Genetic Variant NM_024490.4:c.3510G>C (chr15-25681057-C-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -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

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 made for transcript

Verdict is Benign. Variant got -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 id 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

GnomAD3 exomes

AF:

0.116

AC:

29157

AN:

250822

Hom.:

2213

AF XY:

0.126

AC XY:

17078

AN XY:

135498

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 SAS exome

AF:

0.247

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

Gnomad4 AFR exome

AF:

0.0683

Gnomad4 AMR exome

AF:

0.0516

Gnomad4 ASJ exome

AF:

0.0585

Gnomad4 EAS exome

AF:

0.169

Gnomad4 SAS exome

AF:

0.243

Gnomad4 FIN exome

AF:

0.134

Gnomad4 NFE exome

AF:

0.0947

Gnomad4 OTH exome

AF:

0.110

GnomAD4 genome

AF:

0.0979

AC:

14894

AN:

152136

Hom.:

896

Cov.:

AF XY:

0.103

AC XY:

7681

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.0727

Gnomad4 AMR

AF:

0.0705

Gnomad4 ASJ

AF:

0.0585

Gnomad4 EAS

AF:

0.184

Gnomad4 SAS

AF:

0.255

Gnomad4 FIN

AF:

0.141

Gnomad4 NFE

AF:

0.0970

Gnomad4 OTH

AF:

0.0895

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

DANN

Benign

0.54

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