Genetic Variant ABCE1:p.Ile309Val (chr4-145119934-A-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_002940.3(ABCE1):c.925A>G(p.Ile309Val) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 1/1 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)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ABCE1
NM_002940.3 missense, splice_region

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.26

Publications

0 publications found

Variant links:

Genes affected

ABCE1 (HGNC:69): (ATP binding cassette subfamily E member 1) The protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the OABP subfamily. Alternatively referred to as the RNase L inhibitor, this protein functions to block the activity of ribonuclease L. Activation of ribonuclease L leads to inhibition of protein synthesis in the 2-5A/RNase L system, the central pathway for viral interferon action. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

ABCE1 links:

OTUD4 (HGNC:24949): (OTU deubiquitinase 4) Alternatively spliced transcript variants have been found for this gene. The smaller protein isoform encoded by the shorter transcript variant is found only in HIV-1 infected cells. [provided by RefSeq, Jul 2010]

OTUD4 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002940.3. 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
	ABCE1	NM_002940.3	MANE Select	c.925A>G	p.Ile309Val	missense splice_region	Exon 11 of 18	NP_002931.2	P61221
	ABCE1	NM_001040876.2		c.925A>G	p.Ile309Val	missense splice_region	Exon 11 of 18	NP_001035809.1	P61221

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ABCE1	ENST00000296577.9	TSL:1 MANE Select	c.925A>G	p.Ile309Val	missense splice_region	Exon 11 of 18	ENSP00000296577.4	P61221
ABCE1	ENST00000507193.5	TSL:1	n.925A>G		splice_region non_coding_transcript_exon	Exon 11 of 19	ENSP00000422068.1	D6R9I9
ABCE1	ENST00000877695.1		c.925A>G	p.Ile309Val	missense splice_region	Exon 11 of 18	ENSP00000547754.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1457450

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724944

African (AFR)

AF:

0.00

AC:

AN:

33236

American (AMR)

AF:

0.00

AC:

AN:

44110

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26066

East Asian (EAS)

AF:

0.00

AC:

AN:

39532

South Asian (SAS)

AF:

0.00

AC:

AN:

85128

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53344

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5752

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110102

Other (OTH)

AF:

0.00

AC:

AN:

60180

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

Pathogenic

0.61

BayesDel_addAF

Pathogenic

0.18

BayesDel_noAF

Uncertain

0.030

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.42

Eigen

Uncertain

0.60

Eigen_PC

Uncertain

0.64

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.99

M_CAP

Uncertain

0.11

MetaRNN

Uncertain

0.50

MetaSVM

Uncertain

0.70

MutationAssessor

Uncertain

2.0

PhyloP100

9.3

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-0.92

REVEL

Pathogenic

0.71

Sift

Uncertain

0.0060

Sift4G

Uncertain

0.031

Polyphen

0.94

Vest4

0.45

MutPred

0.41

Gain of helix (P = 0.0696)

MVP

0.88

MPC

1.6

ClinPred

0.91

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.29

gMVP

0.64

Mutation Taster

=76/24

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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