Genetic Variant EVI5:p.Gln579His (chr1-92624266-T-A) – 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_001350197.2(EVI5):c.1737A>T(p.Gln579His) variant causes a missense 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q579R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

EVI5
NM_001350197.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.851

Publications

23 publications found

Variant links:

Genes affected

EVI5 (HGNC:3501): (ecotropic viral integration site 5) Enables GTPase activator activity and small GTPase binding activity. Involved in positive regulation of GTPase activity and retrograde transport, endosome to Golgi. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

EVI5 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, 0.817

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001350197.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EVI5	NM_001350197.2	MANE Select	c.1737A>T	p.Gln579His	missense	Exon 16 of 20	NP_001337126.1	A0A804HIC4
EVI5	NM_001308248.2		c.1722A>T	p.Gln574His	missense	Exon 15 of 19	NP_001295177.1	O60447-2
EVI5	NM_001377210.1		c.1713A>T	p.Gln571His	missense	Exon 15 of 19	NP_001364139.1	A0A9L9PXL1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EVI5	ENST00000684568.2	MANE Select	c.1737A>T	p.Gln579His	missense	Exon 16 of 20	ENSP00000506999.1	A0A804HIC4
EVI5	ENST00000540033.3	TSL:1	c.1722A>T	p.Gln574His	missense	Exon 15 of 19	ENSP00000440826.2	O60447-2
EVI5	ENST00000370331.5	TSL:1	c.1689A>T	p.Gln563His	missense	Exon 14 of 18	ENSP00000359356.1	O60447-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1460810

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726812

African (AFR)

AF:

0.00

AC:

AN:

33464

American (AMR)

AF:

0.00

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39676

South Asian (SAS)

AF:

0.00

AC:

AN:

86238

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53406

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111048

Other (OTH)

AF:

0.00

AC:

AN:

60368

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.48

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Uncertain

-0.050

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

Eigen

Uncertain

0.33

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.027

MetaRNN

Pathogenic

0.82

MetaSVM

Benign

-0.90

MutationAssessor

Pathogenic

3.2

PhyloP100

0.85

PrimateAI

Uncertain

0.68

PROVEAN

Uncertain

-3.3

REVEL

Benign

0.24

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0040

Polyphen

0.98

Vest4

0.76

MutPred

0.11

Loss of MoRF binding (P = 0.0998)

MVP

0.56

MPC

0.39

ClinPred

0.97

GERP RS

2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.55

gMVP

0.51

Mutation Taster

=53/47

polymorphism

(source)

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

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