Genetic Variant NM_006095.2:c.2620A>G (chr4-42455599-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006095.2(ATP8A1):c.2620A>G(p.Ile874Val) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/24 in silico tools predict 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

ATP8A1
NM_006095.2 missense, splice_region

Scores

Splicing: ADA: 0.0001803

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.19

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17349991).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006095.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ATP8A1	NM_006095.2	MANE Select	c.2620A>G	p.Ile874Val	missense splice_region	Exon 28 of 37	NP_006086.1	Q9Y2Q0-1
ATP8A1	NM_001400024.1		c.2620A>G	p.Ile874Val	missense splice_region	Exon 28 of 37	NP_001386953.1
ATP8A1	NM_001400025.1		c.2596A>G	p.Ile866Val	missense splice_region	Exon 28 of 37	NP_001386954.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ATP8A1	ENST00000381668.9	TSL:1 MANE Select	c.2620A>G	p.Ile874Val	missense splice_region	Exon 28 of 37	ENSP00000371084.5	Q9Y2Q0-1
ATP8A1	ENST00000264449.14	TSL:1	c.2575A>G	p.Ile859Val	missense splice_region	Exon 27 of 36	ENSP00000264449.10	Q9Y2Q0-3
ATP8A1	ENST00000514372.5	TSL:1	n.*272A>G		splice_region non_coding_transcript_exon	Exon 5 of 14	ENSP00000426495.1	H0YAA1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.047

BayesDel_noAF

Benign

-0.31

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.078

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.054

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.82

M_CAP

Benign

0.030

MetaRNN

Benign

0.17

MetaSVM

Benign

-0.38

MutationAssessor

Benign

0.075

PhyloP100

2.2

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-0.94

REVEL

Benign

0.29

Sift

Uncertain

0.022

Sift4G

Uncertain

0.025

Polyphen

0.0

Vest4

0.13

MutPred

0.61

Loss of helix (P = 0.079)

MVP

0.30

MPC

0.40

ClinPred

0.47

GERP RS

4.2

Varity_R

0.18

gMVP

0.38

Mutation Taster

=40/60

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00018

dbscSNV1_RF

Benign

0.0040

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over