1-92513741-C-T

Variant names:

• chr1-92513741-C-T
• rs1659409038
• NM_001350197.2:c.2396G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001350197.2(EVI5):​c.2396G>A​(p.Ser799Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 26)
• Consequence: EVI5 NM_001350197.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.586
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.060182333).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001350197.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EVI5	NM_001350197.2	MANE Select	c.2396G>A	p.Ser799Asn	missense	Exon 20 of 20	NP_001337126.1	A0A804HIC4
	EVI5	NM_001308248.2		c.2381G>A	p.Ser794Asn	missense	Exon 19 of 19	NP_001295177.1	O60447-2
	EVI5	NM_001377210.1		c.2372G>A	p.Ser791Asn	missense	Exon 19 of 19	NP_001364139.1	A0A9L9PXL1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EVI5	ENST00000684568.2	MANE Select	c.2396G>A	p.Ser799Asn	missense	Exon 20 of 20	ENSP00000506999.1	A0A804HIC4
	EVI5	ENST00000540033.3	TSL:1	c.2381G>A	p.Ser794Asn	missense	Exon 19 of 19	ENSP00000440826.2	O60447-2
	EVI5	ENST00000370331.5	TSL:1	c.2348G>A	p.Ser783Asn	missense	Exon 18 of 18	ENSP00000359356.1	O60447-1

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 26

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	7.9
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0050	T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.0068	T
MetaRNN	Benign	0.060	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.59
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.19	N
REVEL	Benign	0.10
Sift	Benign	0.083	T
Sift4G	Benign	0.71	T
Polyphen		0.0	B
Vest4		0.067
MutPred		0.037		Loss of phosphorylation at S794 (P = 0.0091)
MVP		0.32
MPC		0.14
ClinPred		0.083	T
GERP RS		4.0
Varity_R		0.064
gMVP		0.23
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

dbSNP: rs1659409038; hg19: chr1-92979298; COSMIC: COSV100945124;