chr7-27243079-G-C

Variant names:

• chr7-27243079-G-C
• rs147870256
• NM_001989.5:c.49G>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001989.5(EVX1):​c.49G>C​(p.Gly17Arg) 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 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. 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.51
• 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.851

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.49G>C	p.Gly17Arg	missense	Exon 1 of 3	NP_001980.1	P49640-1
	EVX1	NM_001304519.2		c.-443G>C		5_prime_UTR	Exon 1 of 3	NP_001291448.1	P49640-2
	EVX1	NM_001304520.2		c.-495G>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.49G>C	p.Gly17Arg	missense	Exon 1 of 3	ENSP00000419266.3	P49640-1
	EVX1	ENST00000222761.7	TSL:1	c.49G>C	p.Gly17Arg	missense	Exon 1 of 3	ENSP00000222761.3	F8W9J5
	EVX1-AS	ENST00000517726.1	TSL:3	n.270-1069C>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459740 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 725984

African (AFR) AF: 0.00 AC: 0 AN: 33354

American (AMR) AF: 0.00 AC: 0 AN: 44522

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26064

East Asian (EAS) AF: 0.00 AC: 0 AN: 39504

South Asian (SAS) AF: 0.00 AC: 0 AN: 85748

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53294

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111180

Other (OTH) AF: 0.00 AC: 0 AN: 60316

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.52
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.10
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.49	T
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.87	D
M_CAP	Pathogenic	0.43	D
MetaRNN	Pathogenic	0.85	D
MetaSVM	Pathogenic	0.82	D
MutationAssessor	Uncertain	2.2	M
PhyloP100		5.5
PrimateAI	Pathogenic	0.81	D
PROVEAN	Pathogenic	-6.7	D
REVEL	Pathogenic	0.79
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.86
MutPred		0.35		Gain of MoRF binding (P = 0.0229)
MVP		0.99
MPC		1.7
ClinPred		0.99	D
GERP RS		4.2
PromoterAI		-0.0044	Neutral
Varity_R		0.60
gMVP		0.34
Mutation Taster		=40/60	disease causing

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: rs147870256; hg19: chr7-27282698;