Genetic Variant NM_001989.5:c.433G>T (chr7-27245053-G-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001989.5(EVX1):c.433G>T(p.Gly145Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000478 in 1,609,834 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000047 ( 0 hom. )

Consequence

EVX1
NM_001989.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.177

Publications

2 publications found

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 links:

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]

EVX1-AS links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07518858).

BS2

High AC in GnomAd4 at 8 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001989.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EVX1	NM_001989.5	MANE Select	c.433G>T	p.Gly145Cys	missense	Exon 2 of 3	NP_001980.1	P49640-1
EVX1	NM_001304519.2		c.-114G>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 3	NP_001291448.1	P49640-2
EVX1	NM_001304520.2		c.-114G>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 4	NP_001291449.1	P49640-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EVX1	ENST00000496902.7	TSL:1 MANE Select	c.433G>T	p.Gly145Cys	missense	Exon 2 of 3	ENSP00000419266.3	P49640-1
EVX1	ENST00000222761.7	TSL:1	c.378G>T	p.Pro126Pro	synonymous	Exon 2 of 3	ENSP00000222761.3	F8W9J5
EVX1	ENST00000580535.1	TSL:2	c.93G>T	p.Pro31Pro	synonymous	Exon 3 of 4	ENSP00000463759.1	J3QQJ1

Frequencies

GnomAD3 genomes

AF:

0.0000525

AC:

AN:

152244

Hom.:

Cov.:

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:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000576

AC:

AN:

243238

AF XY:

0.0000754

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000555

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000109

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.0000473

AC:

AN:

1457590

Hom.:

Cov.:

AF XY:

0.0000441

AC XY:

AN XY:

725112

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33470

American (AMR)

AF:

0.0000224

AC:

AN:

44686

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26088

East Asian (EAS)

AF:

0.00

AC:

AN:

39678

South Asian (SAS)

AF:

0.00

AC:

AN:

86176

European-Finnish (FIN)

AF:

0.0000201

AC:

AN:

49776

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.0000585

AC:

AN:

1111606

Other (OTH)

AF:

0.0000166

AC:

AN:

60348

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000525

AC:

AN:

152244

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41460

American (AMR)

AF:

0.00

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000882

AC:

AN:

68050

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.519

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000180

Hom.:

Bravo

AF:

0.0000264

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000234

AC:

ExAC

AF:

0.0000331

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.18

Eigen

Benign

-0.76

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.59

M_CAP

Benign

0.045

MetaRNN

Benign

0.075

MetaSVM

Benign

-0.42

MutationAssessor

Benign

0.46

PhyloP100

-0.18

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.8

REVEL

Benign

0.12

Sift

Benign

0.21

Sift4G

Benign

0.12

Polyphen

0.052

Vest4

0.099

MVP

0.87

MPC

0.65

ClinPred

0.048

GERP RS

0.72

Varity_R

0.12

gMVP

0.35

Mutation Taster

=90/10

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over