rs2076741

Variant names:

• chr15-25681057-C-G
• rs2076741
• NM_024490.4:c.3510G>C

Your query was ambiguous. Multiple possible variants found:

• chr15-25681057-C-G
• chr15-25681057-C-A
• chr15-25681057-C-T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

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
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.634
• Publications: 8 publications found

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]

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024490.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP10A	NM_024490.4	MANE Select	c.3510G>C	p.Thr1170Thr	synonymous	Exon 18 of 21	NP_077816.1	O60312-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATP10A	ENST00000555815.7	TSL:5 MANE Select	c.3510G>C	p.Thr1170Thr	synonymous	Exon 18 of 21	ENSP00000450480.2	O60312-1
	ATP10A	ENST00000356865.11	TSL:1	c.3510G>C	p.Thr1170Thr	synonymous	Exon 19 of 22	ENSP00000349325.6	O60312-1
	ATP10A	ENST00000555450.2	TSL:3	n.1302G>C		non_coding_transcript_exon	Exon 2 of 5

Frequencies

GnomAD3 genomes AF: 0.0980 AC: 14890 AN: 152016 Hom.: 897 Cov.: 33

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

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.: 36 AF XY: 0.110 AC XY: 80089 AN XY: 725276

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

GnomAD4 genome AF: 0.0979 AC: 14894 AN: 152136 Hom.: 896 Cov.: 33 AF XY: 0.103 AC XY: 7681 AN XY: 74366

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: 40 AN: 294

European-Non Finnish (NFE) AF: 0.0970 AC: 6593 AN: 68000

Other (OTH) AF: 0.0895 AC: 189 AN: 2112

Alfa AF: 0.0590 Hom.: 59

Bravo AF: 0.0881

Asia WGS AF: 0.192 AC: 668 AN: 3478

EpiCase AF: 0.0965

EpiControl AF: 0.101

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	ATP10A-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	0.045
DANN	Benign	0.54
PhyloP100		-0.63
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2076741; hg19: chr15-25926204; COSMIC: COSV63514002; COSMIC: COSV63514002;