7-27243199-A-G

Variant names:

• chr7-27243199-A-G
• rs1783071470
• NM_001989.5:c.169A>G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001989.5(EVX1):​c.169A>G​(p.Thr57Ala) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: EVX1 NM_001989.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.176

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 Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.051196396).
• BP6: Variant 7-27243199-A-G is Benign according to our data. Variant chr7-27243199-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3510762.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EVX1	NM_001989.5	c.169A>G	p.Thr57Ala	missense_variant	Exon 1 of 3	ENST00000496902.7	NP_001980.1
EVX1	NM_001304519.2	c.-323A>G		5_prime_UTR_variant	Exon 1 of 3		NP_001291448.1
EVX1	NM_001304520.2	c.-375A>G		5_prime_UTR_variant	Exon 1 of 4		NP_001291449.1
EVX1-AS	NR_120507.1	n.270-1189T>C		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EVX1	ENST00000496902.7	c.169A>G	p.Thr57Ala	missense_variant	Exon 1 of 3	1	NM_001989.5	ENSP00000419266.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Oct 25, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.051
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	5.8
DANN	Benign	0.85
DEOGEN2	Benign	0.047	.;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.045	N
LIST_S2	Benign	0.42	T;T
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.051	T;T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	-0.35	.;N
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.65	N;N
REVEL	Benign	0.11
Sift	Benign	0.31	T;T
Sift4G	Benign	0.18	T;T
Polyphen		0.0	B;B
Vest4		0.017
MutPred		0.22		Loss of phosphorylation at T57 (P = 0.0016);Loss of phosphorylation at T57 (P = 0.0016);
MVP		0.67
MPC		0.60
ClinPred		0.14	T
GERP RS		-2.6
Varity_R		0.026
gMVP		0.13

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: rs1783071470; hg19: chr7-27282818;