dbSNP rs1283685554: EVI5:p.Cys725Phe (chr1-92513963-C-A) – 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_001350197.2(EVI5):c.2174G>T(p.Cys725Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. C725Y) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

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: 4.70

Publications

0 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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.2174G>T	p.Cys725Phe	missense	Exon 20 of 20	NP_001337126.1	A0A804HIC4
EVI5	NM_001308248.2		c.2159G>T	p.Cys720Phe	missense	Exon 19 of 19	NP_001295177.1	O60447-2
EVI5	NM_001377210.1		c.2150G>T	p.Cys717Phe	missense	Exon 19 of 19	NP_001364139.1	A0A9L9PXL1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EVI5	ENST00000684568.2	MANE Select	c.2174G>T	p.Cys725Phe	missense	Exon 20 of 20	ENSP00000506999.1	A0A804HIC4
EVI5	ENST00000540033.3	TSL:1	c.2159G>T	p.Cys720Phe	missense	Exon 19 of 19	ENSP00000440826.2	O60447-2
EVI5	ENST00000370331.5	TSL:1	c.2126G>T	p.Cys709Phe	missense	Exon 18 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:

1391690

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

684994

African (AFR)

AF:

0.00

AC:

AN:

31484

American (AMR)

AF:

0.00

AC:

AN:

37050

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22240

East Asian (EAS)

AF:

0.00

AC:

AN:

38606

South Asian (SAS)

AF:

0.00

AC:

AN:

74764

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50924

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5440

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1074062

Other (OTH)

AF:

0.00

AC:

AN:

57120

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Uncertain

0.050

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.012

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.92

M_CAP

Benign

0.017

MetaRNN

Uncertain

0.52

MetaSVM

Benign

-1.2

MutationAssessor

Uncertain

2.1

PhyloP100

4.7

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-1.1

REVEL

Benign

0.21

Sift

Benign

0.11

Sift4G

Benign

0.42

Polyphen

0.93

Vest4

0.83

MutPred

0.18

Loss of catalytic residue at L721 (P = 0.0404)

MVP

0.48

MPC

0.57

ClinPred

0.79

GERP RS

5.9

Varity_R

0.39

gMVP

0.47

Mutation Taster

=55/45

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

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