7-27243218-G-A

Variant names:

• chr7-27243218-G-A
• rs1783072602
• NM_001989.5:c.188G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001989.5(EVX1):​c.188G>A​(p.Gly63Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: EVX1 NM_001989.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.88

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15425986).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EVX1	NM_001989.5	c.188G>A	p.Gly63Glu	missense_variant	Exon 1 of 3	ENST00000496902.7	NP_001980.1
EVX1	NM_001304519.2	c.-304G>A		5_prime_UTR_variant	Exon 1 of 3		NP_001291448.1
EVX1	NM_001304520.2	c.-356G>A		5_prime_UTR_variant	Exon 1 of 4		NP_001291449.1
EVX1-AS	NR_120507.1	n.270-1208C>T		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EVX1	ENST00000496902.7	c.188G>A	p.Gly63Glu	missense_variant	Exon 1 of 3	1	NM_001989.5	ENSP00000419266.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1399108 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 690398

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.: 33

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 07, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.188G>A (p.G63E) alteration is located in exon 1 (coding exon 1) of the EVX1 gene. This alteration results from a G to A substitution at nucleotide position 188, causing the glycine (G) at amino acid position 63 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Uncertain	0.067	T
BayesDel_noAF	Benign	-0.14
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.061	.;T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.28
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.74	T;T
M_CAP	Uncertain	0.17	D
MetaRNN	Benign	0.15	T;T
MetaSVM	Uncertain	-0.17	T
MutationAssessor	Benign	1.9	.;M
PrimateAI	Uncertain	0.68	T
PROVEAN	Uncertain	-3.3	D;N
REVEL	Uncertain	0.33
Sift	Benign	0.82	T;T
Sift4G	Benign	0.16	T;T
Polyphen		0.82	P;B
Vest4		0.33
MutPred		0.36		Gain of solvent accessibility (P = 0.0074);Gain of solvent accessibility (P = 0.0074);
MVP		0.91
MPC		1.0
ClinPred		0.81	D
GERP RS		1.1
Varity_R		0.092
gMVP		0.19

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: rs1783072602; hg19: chr7-27282837;