7-27243217-G-C

Variant names:

• chr7-27243217-G-C
• rs993150459
• NM_001989.5:c.187G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001989.5(EVX1):​c.187G>C​(p.Gly63Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G63V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: EVX1 NM_001989.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.85
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2305294).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EVX1	NM_001989.5	MANE Select	c.187G>C	p.Gly63Arg	missense	Exon 1 of 3	NP_001980.1	P49640-1
	EVX1	NM_001304519.2		c.-305G>C		5_prime_UTR	Exon 1 of 3	NP_001291448.1	P49640-2
	EVX1	NM_001304520.2		c.-357G>C		5_prime_UTR	Exon 1 of 4	NP_001291449.1	P49640-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EVX1	ENST00000496902.7	TSL:1 MANE Select	c.187G>C	p.Gly63Arg	missense	Exon 1 of 3	ENSP00000419266.3	P49640-1
	EVX1	ENST00000222761.7	TSL:1	c.187G>C	p.Gly63Arg	missense	Exon 1 of 3	ENSP00000222761.3	F8W9J5
	EVX1-AS	ENST00000517726.1	TSL:3	n.270-1207C>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Uncertain	0.049	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T
Eigen	Benign	0.11
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.79	T
M_CAP	Uncertain	0.17	D
MetaRNN	Benign	0.23	T
MetaSVM	Uncertain	-0.044	T
MutationAssessor	Benign	1.6	L
PhyloP100		4.9
PrimateAI	Uncertain	0.69	T
PROVEAN	Uncertain	-3.9	D
REVEL	Uncertain	0.35
Sift	Benign	0.19	T
Sift4G	Benign	0.16	T
Polyphen		0.035	B
Vest4		0.28
MutPred		0.41		Gain of methylation at G63 (P = 0.0196)
MVP		0.94
MPC		1.2
ClinPred		0.89	D
GERP RS		5.1
PromoterAI		-0.0031	Neutral
Varity_R		0.18
gMVP		0.26
Mutation Taster		=87/13	polymorphism

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

Other links and lift over

dbSNP: rs993150459; hg19: chr7-27282836;