chr14-100123593-T-A

Position:

• chr14-100123593-T-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_016337.3(EVL):​c.413T>A​(p.Ile138Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,461,820 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 0.000012 (0 hom.)
• Consequence: EVL NM_016337.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.68

Genes affected

EVL (HGNC:20234): (Enah/Vasp-like) Predicted to enable SH3 domain binding activity and profilin binding activity. Involved in negative regulation of epithelial cell migration; negative regulation of ruffle assembly; and positive regulation of stress fiber assembly. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.17279914).
• BS2: High AC in GnomAdExome4 at 17 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EVL	NM_016337.3	c.413T>A	p.Ile138Asn	missense_variant	4/14	ENST00000392920.8	NP_057421.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EVL	ENST00000392920.8	c.413T>A	p.Ile138Asn	missense_variant	4/14	1	NM_016337.3	ENSP00000376652	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000116 AC: 17 AN: 1461820 Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8 AN XY: 727212

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: 0.00000989

Gnomad4 OTH exome AF: 0.0000994

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000936 Hom.: 0

Bravo AF: 0.00000756

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 18, 2021

The c.413T>A (p.I138N) alteration is located in exon 4 (coding exon 4) of the EVL gene. This alteration results from a T to A substitution at nucleotide position 413, causing the isoleucine (I) at amino acid position 138 to be replaced by an asparagine (N). 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	0.11
BayesDel_addAF	Benign	-0.0078	T
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.53	D;.;.;T;T
Eigen	Benign	0.14
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Uncertain	0.96	D;D;D;T;D
M_CAP	Benign	0.041	D
MetaRNN	Benign	0.17	T;T;T;T;T
MetaSVM	Benign	-0.76	T
MutationAssessor	Uncertain	2.0	M;.;.;.;.
MutationTaster	Benign	0.86	D;D;D
PrimateAI	Uncertain	0.59	T
PROVEAN	Pathogenic	-4.6	D;D;D;D;N
REVEL	Benign	0.16
Sift	Benign	0.067	T;T;D;D;D
Sift4G	Benign	0.29	T;T;T;T;T
Polyphen		0.74	P;.;B;.;.
Vest4		0.48
MutPred		0.29		Gain of catalytic residue at M134 (P = 0.0645);.;.;.;.;
MVP		0.48
MPC		0.83
ClinPred		0.99	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.36
gMVP		0.23

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: rs1887837386; hg19: chr14-100589930;