Variant chr19-7862240-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001159944.3(EVI5L):c.1763G>A(p.Arg588His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000704 in 1,421,270 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

EVI5L
NM_001159944.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.21

Variant links:

Genes affected

EVI5L (HGNC:30464): (ecotropic viral integration site 5 like) Enables GTPase activator activity and small GTPase binding activity. Involved in negative regulation of cilium assembly and positive regulation of GTPase activity. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

EVI5L links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.27009228).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EVI5L	NM_001159944.3 link	c.1763G>A	p.Arg588His	missense_variant	16/20	ENST00000538904.7	NP_001153416.1	Q96CN4-2
EVI5L	NM_145245.5 link	c.1730G>A	p.Arg577His	missense_variant	15/19		NP_660288.1	Q96CN4-1A0A384MR55

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
EVI5L	ENST00000538904.7 link	c.1763G>A	p.Arg588His	missense_variant	16/20	1	NM_001159944.3	ENSP00000445905.1	Q96CN4-2
EVI5L	ENST00000270530.8 link	c.1730G>A	p.Arg577His	missense_variant	15/19	1		ENSP00000270530.3	Q96CN4-1
EVI5L	ENST00000601766.1 link	c.246+222G>A		intron_variant		3		ENSP00000470145.1	M0QYX4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.04e-7

AC:

AN:

1421270

Hom.:

Cov.:

AF XY:

0.00000142

AC XY:

AN XY:

703358

show subpopulations

Gnomad4 AFR exome

AF:

0.0000305

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 17, 2023

The c.1763G>A (p.R588H) alteration is located in exon 15 (coding exon 15) of the EVI5L gene. This alteration results from a G to A substitution at nucleotide position 1763, causing the arginine (R) at amino acid position 588 to be replaced by a histidine (H). 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

0.14

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.23

T;.

Eigen

Uncertain

0.39

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Benign

0.50

LIST_S2

Uncertain

0.94

D;D

M_CAP

Pathogenic

0.48

MetaRNN

Benign

0.27

T;T

MetaSVM

Benign

-0.65

MutationAssessor

Uncertain

2.6

M;.

PrimateAI

Pathogenic

0.90

PROVEAN

Uncertain

-3.3

D;D

REVEL

Benign

0.067

Sift

Uncertain

0.0040

D;D

Sift4G

Uncertain

0.0070

D;D

Polyphen

1.0

D;.

Vest4

0.13

MutPred

0.24

Loss of methylation at R577 (P = 0.0343);.;

MVP

0.51

MPC

2.1

ClinPred

0.97

GERP RS

3.6

Varity_R

0.25

gMVP

0.29

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

LitVar

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over