rs1283685554

Variant names:

• chr1-92513963-C-A
• rs1283685554
• NM_001350197.2:c.2174G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-92513963-C-A
• chr1-92513963-C-T

Variant summary

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

The NM_001350197.2(EVI5):​c.2174G>T​(p.Cys725Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C725Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: EVI5 NM_001350197.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.70

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 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 rank	MANE	Protein	UniProt
EVI5	NM_001350197.2	c.2174G>T	p.Cys725Phe	missense_variant	Exon 20 of 20	ENST00000684568.2	NP_001337126.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EVI5	ENST00000684568.2	c.2174G>T	p.Cys725Phe	missense_variant	Exon 20 of 20		NM_001350197.2	ENSP00000506999.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1391690 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 684994

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.012	T;.
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.92	D;D
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.52	D;D
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.1	M;.
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-1.1	N;.
REVEL	Benign	0.21
Sift	Benign	0.11	T;.
Sift4G	Benign	0.42	T;T
Polyphen		0.93	P;.
Vest4		0.83
MutPred		0.18		.;Loss of catalytic residue at L721 (P = 0.0404);
MVP		0.48
MPC		0.57
ClinPred		0.79	D
GERP RS		5.9
Varity_R		0.39
gMVP		0.47

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

Other links and lift over

dbSNP: rs1283685554; hg19: chr1-92979520;