1-92624283-C-T

Position:

• chr1-92624283-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001350197.2(EVI5):​c.1720G>A​(p.Ala574Thr) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 29)
• Consequence: EVI5 NM_001350197.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.454

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.058908373).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EVI5	NM_001350197.2	c.1720G>A	p.Ala574Thr	missense_variant	16/20	ENST00000684568.2	NP_001337126.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EVI5	ENST00000684568.2	c.1720G>A	p.Ala574Thr	missense_variant	16/20		NM_001350197.2	ENSP00000506999	P1

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 29

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

Jan 24, 2023

The c.1672G>A (p.A558T) alteration is located in exon 14 (coding exon 14) of the EVI5 gene. This alteration results from a G to A substitution at nucleotide position 1672, causing the alanine (A) at amino acid position 558 to be replaced by a threonine (T). 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	0.064
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	14
DANN	Benign	0.96
DEOGEN2	Benign	0.0036	T;.
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.85	T;T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.059	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.23	N;.
MutationTaster	Benign	0.97	D;D;D
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.050	N;.
REVEL	Benign	0.068
Sift	Benign	0.45	T;.
Sift4G	Benign	0.70	T;T
Polyphen		0.0	B;.
Vest4		0.063
MutPred		0.11		.;Gain of phosphorylation at A569 (P = 0.0267);
MVP		0.33
MPC		0.15
ClinPred		0.29	T
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.081
gMVP		0.083

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: chr1-93089840;