NM_006095.2:c.1948-4765G>T

Variant names:

• chr4-42511919-C-A
• rs10517039
• NM_006095.2:c.1948-4765G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006095.2(ATP8A1):​c.1948-4765G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0786 in 152,054 control chromosomes in the GnomAD database, including 626 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.079 (626 hom., cov: 32)
• Consequence: ATP8A1 NM_006095.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.364
• Publications: 4 publications found

Genes affected

ATP8A1 (HGNC:13531): (ATPase phospholipid transporting 8A1) The P-type adenosinetriphosphatases (P-type ATPases) are a family of proteins which use the free energy of ATP hydrolysis to drive uphill transport of ions across membranes. Several subfamilies of P-type ATPases have been identified. One subfamily catalyzes transport of heavy metal ions. Another subfamily transports non-heavy metal ions (NMHI). The protein encoded by this gene is a member of the third subfamily of P-type ATPases and acts to transport amphipaths, such as phosphatidylserine. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP8A1	NM_006095.2	c.1948-4765G>T		intron_variant	Intron 22 of 36	ENST00000381668.9	NP_006086.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP8A1	ENST00000381668.9	c.1948-4765G>T		intron_variant	Intron 22 of 36	1	NM_006095.2	ENSP00000371084.5
ATP8A1	ENST00000264449.14	c.1903-4765G>T		intron_variant	Intron 21 of 35	1		ENSP00000264449.10
ATP8A1	ENST00000700470.1	c.1903-4765G>T		intron_variant	Intron 21 of 35			ENSP00000515003.1

Frequencies

GnomAD3 genomes AF: 0.0784 AC: 11911 AN: 151936 Hom.: 621 Cov.: 32

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.244

Gnomad AMR AF: 0.0756

Gnomad ASJ AF: 0.0406

Gnomad EAS AF: 0.0275

Gnomad SAS AF: 0.0627

Gnomad FIN AF: 0.0384

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0467

Gnomad OTH AF: 0.0684

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0786 AC: 11948 AN: 152054 Hom.: 626 Cov.: 32 AF XY: 0.0771 AC XY: 5727 AN XY: 74328

African (AFR) AF: 0.150 AC: 6232 AN: 41436

American (AMR) AF: 0.0762 AC: 1165 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0406 AC: 141 AN: 3470

East Asian (EAS) AF: 0.0276 AC: 143 AN: 5184

South Asian (SAS) AF: 0.0625 AC: 301 AN: 4816

European-Finnish (FIN) AF: 0.0384 AC: 406 AN: 10562

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0467 AC: 3174 AN: 67990

Other (OTH) AF: 0.0724 AC: 153 AN: 2112

Alfa AF: 0.0711 Hom.: 89

Bravo AF: 0.0855

Asia WGS AF: 0.108 AC: 374 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.0
DANN	Benign	0.64
PhyloP100		-0.36
Mutation Taster		=100/0	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: rs10517039; hg19: chr4-42513936;