19-7851700-G-C

Position:

• chr19-7851700-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001159944.3(EVI5L):​c.917G>C​(p.Arg306Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: EVI5L NM_001159944.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.99

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.832

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EVI5L	NM_001159944.3	c.917G>C	p.Arg306Pro	missense_variant	8/20	ENST00000538904.7	NP_001153416.1
EVI5L	NM_145245.5	c.917G>C	p.Arg306Pro	missense_variant	8/19		NP_660288.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EVI5L	ENST00000538904.7	c.917G>C	p.Arg306Pro	missense_variant	8/20	1	NM_001159944.3	ENSP00000445905.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 60

GnomAD4 genome Cov.: 34

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

Jul 07, 2024

The c.917G>C (p.R306P) alteration is located in exon 7 (coding exon 7) of the EVI5L gene. This alteration results from a G to C substitution at nucleotide position 917, causing the arginine (R) at amino acid position 306 to be replaced by a proline (P). 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	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.17
CADD	Pathogenic	31
DANN	Uncertain	1.0
DEOGEN2	Benign	0.39	T;.;T
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.99	D;D;D
M_CAP	Benign	0.027	D
MetaRNN	Pathogenic	0.83	D;D;D
MetaSVM	Benign	-0.58	T
MutationAssessor	Pathogenic	3.6	H;H;.
PrimateAI	Uncertain	0.72	T
PROVEAN	Pathogenic	-5.4	D;D;.
REVEL	Uncertain	0.59
Sift	Uncertain	0.0030	D;D;.
Sift4G	Uncertain	0.0040	D;D;D
Polyphen		0.12	B;.;.
Vest4		0.95
MutPred		0.66		Loss of methylation at R306 (P = 0.0438);Loss of methylation at R306 (P = 0.0438);.;
MVP		0.75
MPC		1.5
ClinPred		0.99	D
GERP RS		4.3
Varity_R		0.92
gMVP		0.96

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-7916586;