Variant 19-7858270-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001159944.3(EVI5L):c.1313G>A(p.Ser438Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000837 in 1,554,090 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000078 ( 0 hom. )

Consequence

EVI5L
NM_001159944.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.371

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.059663773).

BS2

High AC in GnomAdExome4 at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EVI5L	NM_001159944.3 link	c.1313G>A	p.Ser438Asn	missense_variant	13/20	ENST00000538904.7	NP_001153416.1	Q96CN4-2
EVI5L	NM_145245.5 link	c.1280G>A	p.Ser427Asn	missense_variant	12/19		NP_660288.1	Q96CN4-1A0A384MR55

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
EVI5L	ENST00000538904.7 link	c.1313G>A	p.Ser438Asn	missense_variant	13/20	1	NM_001159944.3	ENSP00000445905.1	Q96CN4-2
EVI5L	ENST00000270530.8 link	c.1280G>A	p.Ser427Asn	missense_variant	12/19	1		ENSP00000270530.3	Q96CN4-1
EVI5L	ENST00000600802.1 link	n.78G>A		non_coding_transcript_exon_variant	1/2	1
EVI5L	ENST00000601984.1 link	n.1684G>A		non_coding_transcript_exon_variant	6/6	2

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152208

Hom.:

Cov.:

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:

0.000386

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000626

AC:

AN:

159858

Hom.:

AF XY:

0.0000118

AC XY:

AN XY:

84860

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000842

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000785

AC:

AN:

1401882

Hom.:

Cov.:

AF XY:

0.00000867

AC XY:

AN XY:

692026

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000303

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

AF:

0.0000131

AC:

AN:

152208

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.00000917

AC:

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

Dec 15, 2023

The c.1313G>A (p.S438N) alteration is located in exon 12 (coding exon 12) of the EVI5L gene. This alteration results from a G to A substitution at nucleotide position 1313, causing the serine (S) at amino acid position 438 to be replaced by an asparagine (N). 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

0.11

BayesDel_addAF

Benign

-0.069

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.033

T;.

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.29

FATHMM_MKL

Benign

0.27

LIST_S2

Benign

0.83

T;T

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.060

T;T

MetaSVM

Uncertain

-0.17

MutationAssessor

Benign

1.2

L;.

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-0.76

N;N

REVEL

Benign

0.10

Sift

Benign

0.50

T;T

Sift4G

Benign

0.48

T;T

Polyphen

0.0

B;.

Vest4

0.081

MutPred

0.23

Gain of MoRF binding (P = 0.097);.;

MVP

0.59

MPC

0.91

ClinPred

0.10

GERP RS

5.0

Varity_R

0.098

gMVP

0.12

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