dbSNP rs147870256: EVX1:p.Gly17Ser (chr7-27243079-G-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001989.5(EVX1):c.49G>A(p.Gly17Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,740 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign 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. G17C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

EVX1
NM_001989.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.51

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3110827).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EVX1	NM_001989.5 link	c.49G>A	p.Gly17Ser	missense_variant	Exon 1 of 3	ENST00000496902.7	NP_001980.1	P49640-1
EVX1	NM_001304519.2 link	c.-443G>A		5_prime_UTR_variant	Exon 1 of 3		NP_001291448.1	P49640-2B4DRC0
EVX1	NM_001304520.2 link	c.-495G>A		5_prime_UTR_variant	Exon 1 of 4		NP_001291449.1	P49640-2B4DRC0
EVX1-AS	NR_120507.1 link	n.270-1069C>T		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EVX1	ENST00000496902.7 link	c.49G>A	p.Gly17Ser	missense_variant	Exon 1 of 3	1	NM_001989.5	ENSP00000419266.3		P49640-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000406

AC:

AN:

246112

Hom.:

AF XY:

0.00

AC XY:

AN XY:

133346

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:

0.00000900

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459740

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725984

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

-0.070

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.13

.;T

Eigen

Benign

0.19

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.76

T;T

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.31

T;T

MetaSVM

Uncertain

0.19

MutationAssessor

Uncertain

2.2

.;M

PrimateAI

Uncertain

0.74

PROVEAN

Pathogenic

-5.0

D;N

REVEL

Uncertain

0.47

Sift

Pathogenic

0.0

D;T

Sift4G

Pathogenic

0.0

D;T

Polyphen

0.82

P;P

Vest4

0.90

MutPred

0.23

Gain of sheet (P = 0.0125);Gain of sheet (P = 0.0125);

MVP

0.96

MPC

1.6

ClinPred

0.93

GERP RS

4.2

Varity_R

0.13

gMVP

0.26

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over