NM_001989.5:c.611G>A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001989.5(EVX1):​c.611G>A​(p.Arg204Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000143 in 1,613,468 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R204L) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

EVX1
NM_001989.5 missense

Scores

8
4
4

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.97
Variant links:
Genes affected
EVX1 (HGNC:3506): (even-skipped homeobox 1) This gene encodes a member of the even-skipped homeobox family characterized by the presence of a homeodomain closely related to the Drosophila even-skipped (eve) segmentation gene of the pair-rule class. The encoded protein may play an important role as a transcriptional repressor during embryogenesis. [provided by RefSeq, Jul 2008]
EVX1-AS (HGNC:40223): (EVX1 antisense RNA) Predicted to enable chromatin binding activity. Predicted to be part of histone methyltransferase complex. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2
High AC in GnomAdExome4 at 21 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
EVX1NM_001989.5 linkc.611G>A p.Arg204Gln missense_variant Exon 2 of 3 ENST00000496902.7 NP_001980.1 P49640-1
EVX1NM_001304519.2 linkc.65G>A p.Arg22Gln missense_variant Exon 2 of 3 NP_001291448.1 P49640-2B4DRC0
EVX1NM_001304520.2 linkc.65G>A p.Arg22Gln missense_variant Exon 3 of 4 NP_001291449.1 P49640-2B4DRC0
EVX1-ASNR_120507.1 linkn.269+1730C>T intron_variant Intron 1 of 3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
EVX1ENST00000496902.7 linkc.611G>A p.Arg204Gln missense_variant Exon 2 of 3 1 NM_001989.5 ENSP00000419266.3 P49640-1
EVX1ENST00000222761.7 linkc.556G>A p.Gly186Arg missense_variant Exon 2 of 3 1 ENSP00000222761.3 F8W9J5
EVX1ENST00000580535.1 linkc.271G>A p.Gly91Arg missense_variant Exon 3 of 4 2 ENSP00000463759.1 J3QQJ1
EVX1-ASENST00000517726.1 linkn.269+1730C>T intron_variant Intron 1 of 3 3

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152236
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000120
AC:
3
AN:
249680
Hom.:
0
AF XY:
0.0000221
AC XY:
3
AN XY:
135472
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000266
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000144
AC:
21
AN:
1461232
Hom.:
0
Cov.:
32
AF XY:
0.0000151
AC XY:
11
AN XY:
726938
show subpopulations
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:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000171
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152236
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74366
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000264
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.81
BayesDel_addAF
Pathogenic
0.21
D
BayesDel_noAF
Uncertain
0.13
CADD
Pathogenic
34
DANN
Pathogenic
1.0
Eigen
Uncertain
0.63
Eigen_PC
Pathogenic
0.69
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Benign
0.39
T;.
M_CAP
Uncertain
0.087
D
MetaRNN
Uncertain
0.58
D;D
MetaSVM
Pathogenic
0.94
D
PROVEAN
Benign
1.9
N;.
REVEL
Benign
0.25
Sift
Pathogenic
0.0
D;.
Sift4G
Pathogenic
0.0
D;D
Polyphen
1.0
D;.
Vest4
0.69
MutPred
0.17
Gain of methylation at G186 (P = 0.0227);.;
MVP
0.57
ClinPred
0.99
D
GERP RS
5.5

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs368325052; hg19: chr7-27284850; API