7-27243235-C-T

Variant names:

• chr7-27243235-C-T
• rs1033939449
• NM_001989.5:c.205C>T

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.205C>T​(p.Pro69Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000716 in 1,396,504 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: EVX1 NM_001989.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.255
• 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=0.11798376).

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.205C>T	p.Pro69Ser	missense	Exon 1 of 3	NP_001980.1	P49640-1
	EVX1	NM_001304519.2		c.-287C>T		5_prime_UTR	Exon 1 of 3	NP_001291448.1	P49640-2
	EVX1	NM_001304520.2		c.-339C>T		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.205C>T	p.Pro69Ser	missense	Exon 1 of 3	ENSP00000419266.3	P49640-1
	EVX1	ENST00000222761.7	TSL:1	c.205C>T	p.Pro69Ser	missense	Exon 1 of 3	ENSP00000222761.3	F8W9J5
	EVX1-AS	ENST00000517726.1	TSL:3	n.270-1225G>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.16e-7 AC: 1 AN: 1396504 Hom.: 0 Cov.: 31 AF XY: 0.00000145 AC XY: 1 AN XY: 688942

African (AFR) AF: 0.00 AC: 0 AN: 31518

American (AMR) AF: 0.0000282 AC: 1 AN: 35522

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25036

East Asian (EAS) AF: 0.00 AC: 0 AN: 35672

South Asian (SAS) AF: 0.00 AC: 0 AN: 79602

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47216

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5310

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078786

Other (OTH) AF: 0.00 AC: 0 AN: 57842

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	10
DANN	Benign	0.93
DEOGEN2	Benign	0.044	T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.55
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.55	T
M_CAP	Uncertain	0.24	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.47	T
MutationAssessor	Benign	1.0	L
PhyloP100		0.26
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.70	N
REVEL	Benign	0.17
Sift	Benign	0.093	T
Sift4G	Benign	0.24	T
Polyphen		0.055	B
Vest4		0.050
MutPred		0.15		Gain of phosphorylation at P69 (P = 0.0089)
MVP		0.90
MPC		0.62
ClinPred		0.046	T
GERP RS		-0.20
PromoterAI		-0.045	Neutral
Varity_R		0.088
gMVP		0.21
Mutation Taster		=94/6	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: rs1033939449; hg19: chr7-27282854;