1-92513798-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001350197.2(EVI5):​c.2339G>A​(p.Gly780Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000161 in 1,613,076 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. G780G) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

EVI5
NM_001350197.2 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.558
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.055012137).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
EVI5NM_001350197.2 linkc.2339G>A p.Gly780Asp missense_variant Exon 20 of 20 ENST00000684568.2 NP_001337126.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
EVI5ENST00000684568.2 linkc.2339G>A p.Gly780Asp missense_variant Exon 20 of 20 NM_001350197.2 ENSP00000506999.1 A0A804HIC4

Frequencies

GnomAD3 genomes
AF:
0.00000661
AC:
1
AN:
151348
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000171
AC:
25
AN:
1461728
Hom.:
0
Cov.:
33
AF XY:
0.0000110
AC XY:
8
AN XY:
727160
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000225
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000661
AC:
1
AN:
151348
Hom.:
0
Cov.:
31
AF XY:
0.0000135
AC XY:
1
AN XY:
73856
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 08, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.2291G>A (p.G764D) alteration is located in exon 18 (coding exon 18) of the EVI5 gene. This alteration results from a G to A substitution at nucleotide position 2291, causing the glycine (G) at amino acid position 764 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.079
BayesDel_addAF
Benign
-0.26
T
BayesDel_noAF
Benign
-0.61
CADD
Benign
13
DANN
Benign
0.96
DEOGEN2
Benign
0.0075
T;.
Eigen
Benign
-0.86
Eigen_PC
Benign
-0.86
FATHMM_MKL
Benign
0.12
N
LIST_S2
Benign
0.63
T;T
M_CAP
Benign
0.0058
T
MetaRNN
Benign
0.055
T;T
MetaSVM
Benign
-0.91
T
MutationAssessor
Benign
1.8
L;.
PrimateAI
Benign
0.40
T
PROVEAN
Benign
-0.54
N;N
REVEL
Benign
0.086
Sift
Benign
0.056
T;T
Sift4G
Benign
0.061
T;T
Polyphen
0.0010
B;.
Vest4
0.084
MutPred
0.12
.;Loss of glycosylation at S774 (P = 0.0398);
MVP
0.17
MPC
0.20
ClinPred
0.042
T
GERP RS
-0.76
Varity_R
0.057
gMVP
0.37

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.17
Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1367411605; hg19: chr1-92979355; API