Genetic Variant NM_002940.3:c.708T>G (chr4-145111062-T-G) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_002940.3(ABCE1):c.708T>G(p.Asp236Glu) 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 pathogenic 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 (no stars).

Frequency

Genomes: not found (cov: 32)

Consequence

ABCE1
NM_002940.3 missense, splice_region

Scores

Splicing: ADA: 0.0007849

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 1.38

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 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.745

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.708T>G	p.Asp236Glu	missense splice_region	Exon 8 of 18	NP_002931.2	P61221
	ABCE1	NM_001040876.2		c.708T>G	p.Asp236Glu	missense splice_region	Exon 8 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.708T>G	p.Asp236Glu	missense splice_region	Exon 8 of 18	ENSP00000296577.4	P61221
ABCE1	ENST00000507193.5	TSL:1	n.708T>G		splice_region non_coding_transcript_exon	Exon 8 of 19	ENSP00000422068.1	D6R9I9
ABCE1	ENST00000877695.1		c.708T>G	p.Asp236Glu	missense splice_region	Exon 8 of 18	ENSP00000547754.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

Prostate cancer (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.49

BayesDel_addAF

Pathogenic

0.18

BayesDel_noAF

Uncertain

0.020

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Pathogenic

0.89

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.13

FATHMM_MKL

Uncertain

0.94

LIST_S2

Pathogenic

0.98

M_CAP

Benign

0.085

MetaRNN

Pathogenic

0.75

MetaSVM

Benign

-0.38

MutationAssessor

Benign

0.85

PhyloP100

1.4

PrimateAI

Pathogenic

0.89

PROVEAN

Uncertain

-3.0

REVEL

Uncertain

0.54

Sift

Benign

0.10

Sift4G

Benign

0.078

Polyphen

0.095

Vest4

0.72

MutPred

0.50

Gain of catalytic residue at D236 (P = 0.1623)

MVP

0.96

MPC

1.2

ClinPred

0.70

GERP RS

1.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.26

gMVP

0.83

Mutation Taster

=23/77

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00078

dbscSNV1_RF

Benign

0.33

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