19-7860588-G-A

Position:

• chr19-7860588-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001159944.3(EVI5L):​c.1402G>A​(p.Val468Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000207 in 1,446,354 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: EVI5L NM_001159944.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.94

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EVI5L	NM_001159944.3	c.1402G>A	p.Val468Met	missense_variant	14/20	ENST00000538904.7	NP_001153416.1
EVI5L	NM_145245.5	c.1369G>A	p.Val457Met	missense_variant	13/19		NP_660288.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EVI5L	ENST00000538904.7	c.1402G>A	p.Val468Met	missense_variant	14/20	1	NM_001159944.3	ENSP00000445905.1
EVI5L	ENST00000270530.8	c.1369G>A	p.Val457Met	missense_variant	13/19	1		ENSP00000270530.3
EVI5L	ENST00000601766.1	c.4G>A	p.Val2Met	missense_variant	1/4	3		ENSP00000470145.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000207 AC: 3 AN: 1446354 Hom.: 0 Cov.: 30 AF XY: 0.00000278 AC XY: 2 AN XY: 718186

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: 0.00000271

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 17, 2022

The c.1402G>A (p.V468M) alteration is located in exon 13 (coding exon 13) of the EVI5L gene. This alteration results from a G to A substitution at nucleotide position 1402, causing the valine (V) at amino acid position 468 to be replaced by a methionine (M). 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	Uncertain	0.55
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.17
CADD	Pathogenic	32
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.069	T;.;T
Eigen	Pathogenic	0.78
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.93	D;D;T
M_CAP	Uncertain	0.14	D
MetaRNN	Uncertain	0.72	D;D;D
MetaSVM	Pathogenic	1.1	D
MutationAssessor	Uncertain	2.4	M;.;.
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-2.1	N;N;.
REVEL	Uncertain	0.33
Sift	Uncertain	0.0010	D;D;.
Sift4G	Uncertain	0.012	D;D;D
Polyphen		1.0	D;.;.
Vest4		0.80
MutPred		0.29		Gain of phosphorylation at T462 (P = 0.0939);.;.;
MVP		0.88
MPC		2.1
ClinPred		0.98	D
GERP RS		4.4
Varity_R		0.42
gMVP		0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-7925474;