Variant 4-42422903-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_006095.2(ATP8A1):c.3213-4G>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00019 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ATP8A1
NM_006095.2 splice_region, intron

Scores

Splicing: ADA: 0.00001787

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.476

Variant links:

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]

ATP8A1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 4-42422903-C-A is Benign according to our data. Variant chr4-42422903-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 771141.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP8A1	NM_006095.2 linkuse as main transcript	c.3213-4G>T		splice_region_variant, intron_variant		ENST00000381668.9	NP_006086.1	Q9Y2Q0-1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
ATP8A1	ENST00000381668.9 linkuse as main transcript	c.3213-4G>T	splice_region_variant, intron_variant	1	NM_006095.2	ENSP00000371084.5	Q9Y2Q0-1
ATP8A1	ENST00000264449.14 linkuse as main transcript	c.3168-4G>T	splice_region_variant, intron_variant	1		ENSP00000264449.10	Q9Y2Q0-3
ATP8A1	ENST00000514372.5 linkuse as main transcript	n.*865-4G>T	splice_region_variant, intron_variant	1		ENSP00000426495.1	H0YAA1
ATP8A1	ENST00000700470.1 linkuse as main transcript	c.3168-4G>T	splice_region_variant, intron_variant			ENSP00000515003.1	Q9Y2Q0-2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

150034

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000204

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000483

GnomAD3 exomes

AF:

0.000425

AC:

AN:

221218

Hom.:

AF XY:

0.000357

AC XY:

AN XY:

120430

show subpopulations

Gnomad AFR exome

AF:

0.000267

Gnomad AMR exome

AF:

0.000956

Gnomad ASJ exome

AF:

0.000788

Gnomad EAS exome

AF:

0.000500

Gnomad SAS exome

AF:

0.000395

Gnomad FIN exome

AF:

0.0000541

Gnomad NFE exome

AF:

0.000317

Gnomad OTH exome

AF:

0.000770

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000192

AC:

273

AN:

1425574

Hom.:

Cov.:

AF XY:

0.000172

AC XY:

122

AN XY:

709296

show subpopulations

Gnomad4 AFR exome

AF:

0.000769

Gnomad4 AMR exome

AF:

0.00284

Gnomad4 ASJ exome

AF:

0.000479

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000348

Gnomad4 FIN exome

AF:

0.0000204

Gnomad4 NFE exome

AF:

0.0000737

Gnomad4 OTH exome

AF:

0.000289

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000200

AC:

AN:

150034

Hom.:

Cov.:

AF XY:

0.0000137

AC XY:

AN XY:

73072

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000204

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000483

Alfa

AF:

0.00166

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.54

DANN

Benign

0.44

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000018

dbscSNV1_RF

Benign

0.0

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