chr7-27246010-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PP3_Moderate

The NM_001989.5(EVX1):​c.809C>T​(p.Pro270Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000005 in 1,599,928 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 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. P270H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

EVX1
NM_001989.5 missense

Scores

12
6
1

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.47
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 Uncertain_significance. Variant got 2 ACMG points.

PP3
MetaRNN computational evidence supports a deleterious effect, 0.877

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
EVX1NM_001989.5 linkc.809C>T p.Pro270Leu missense_variant Exon 3 of 3 ENST00000496902.7 NP_001980.1 P49640-1
EVX1NM_001304519.2 linkc.263C>T p.Pro88Leu missense_variant Exon 3 of 3 NP_001291448.1 P49640-2B4DRC0
EVX1NM_001304520.2 linkc.263C>T p.Pro88Leu missense_variant Exon 4 of 4 NP_001291449.1 P49640-2B4DRC0
EVX1-ASNR_120507.1 linkn.269+951G>A intron_variant Intron 1 of 3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
EVX1ENST00000496902.7 linkc.809C>T p.Pro270Leu missense_variant Exon 3 of 3 1 NM_001989.5 ENSP00000419266.3 P49640-1
EVX1ENST00000222761.7 linkc.*148C>T 3_prime_UTR_variant Exon 3 of 3 1 ENSP00000222761.3 F8W9J5
EVX1ENST00000580535.1 linkc.*148C>T 3_prime_UTR_variant Exon 4 of 4 2 ENSP00000463759.1 J3QQJ1
EVX1-ASENST00000517726.1 linkn.269+951G>A intron_variant Intron 1 of 3 3

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152172
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000386
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000217
AC:
5
AN:
230096
Hom.:
0
AF XY:
0.0000236
AC XY:
3
AN XY:
127068
show subpopulations
Gnomad AFR exome
AF:
0.0000694
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000227
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000276
AC:
4
AN:
1447756
Hom.:
0
Cov.:
31
AF XY:
0.00000416
AC XY:
3
AN XY:
720812
show subpopulations
Gnomad4 AFR exome
AF:
0.0000598
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000504
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
AF:
0.0000263
AC:
4
AN:
152172
Hom.:
0
Cov.:
33
AF XY:
0.0000135
AC XY:
1
AN XY:
74336
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000386
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000302
ExAC
AF:
0.00000830
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.77
BayesDel_addAF
Pathogenic
0.23
D
BayesDel_noAF
Pathogenic
0.39
CADD
Pathogenic
31
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.55
D
Eigen
Pathogenic
0.78
Eigen_PC
Pathogenic
0.75
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.97
D
M_CAP
Pathogenic
0.71
D
MetaRNN
Pathogenic
0.88
D
MetaSVM
Pathogenic
0.94
D
MutationAssessor
Uncertain
2.3
M
PrimateAI
Pathogenic
0.83
D
PROVEAN
Pathogenic
-7.4
D
REVEL
Pathogenic
0.74
Sift
Uncertain
0.0070
D
Sift4G
Uncertain
0.0020
D
Polyphen
1.0
D
Vest4
0.80
MutPred
0.32
Loss of disorder (P = 0.0171);
MVP
0.98
MPC
1.6
ClinPred
0.95
D
GERP RS
5.3
Varity_R
0.69
gMVP
0.81

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: rs772959917; hg19: chr7-27285629; API