Genetic Variant ENAH:p.Pro352Leu (chr1-225514759-G-A) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_018212.6(ENAH):c.1055C>T(p.Pro352Leu) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 19)

Exomes 𝑓: 0.0000024 ( 0 hom. )

Consequence

ENAH
NM_018212.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.63

Publications

1 publications found

Variant links:

Genes affected

ENAH (HGNC:18271): (ENAH actin regulator) This gene encodes a member of the enabled/ vasodilator-stimulated phosphoprotein. Members of this gene family are involved in actin-based motility. This protein is involved in regulating the assembly of actin filaments and modulates cell adhesion and motility. Alternate splice variants of this gene have been correlated with tumor invasiveness in certain tissues and these variants may serve as prognostic markers. A pseudogene of this gene is found on chromosome 3. [provided by RefSeq, Sep 2016]

ENAH links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.3521338).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ENAH	NM_018212.6 link	c.1055C>T	p.Pro352Leu	missense_variant	Exon 7 of 14	ENST00000366843.7	NP_060682.2	Q8N8S7-2A0A4D6J698

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENAH	ENST00000366843.7 link	c.1055C>T	p.Pro352Leu	missense_variant	Exon 7 of 14	1	NM_018212.6	ENSP00000355808.2		Q8N8S7-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000236

AC:

AN:

1272540

Hom.:

Cov.:

AF XY:

0.00000314

AC XY:

AN XY:

636338

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26420

American (AMR)

AF:

0.00

AC:

AN:

28482

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21618

East Asian (EAS)

AF:

0.00

AC:

AN:

31742

South Asian (SAS)

AF:

0.00

AC:

AN:

76278

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49120

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3674

European-Non Finnish (NFE)

AF:

0.00000305

AC:

AN:

983304

Other (OTH)

AF:

0.00

AC:

AN:

51902

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.542

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 20, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1055C>T (p.P352L) alteration is located in exon 7 (coding exon 7) of the ENAH gene. This alteration results from a C to T substitution at nucleotide position 1055, causing the proline (P) at amino acid position 352 to be replaced by a leucine (L). 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

-0.045

BayesDel_noAF

Benign

-0.30

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.51

D;.;.

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.73

T;D;T

M_CAP

Uncertain

0.29

MetaRNN

Benign

0.35

T;T;T

MetaSVM

Uncertain

0.35

MutationAssessor

Uncertain

2.7

M;.;M

PhyloP100

4.6

PrimateAI

Uncertain

0.77

PROVEAN

Pathogenic

-4.8

D;.;D

REVEL

Uncertain

0.32

Sift

Pathogenic

0.0

D;.;D

Sift4G

Benign

0.10

T;T;T

Polyphen

1.0

D;.;D

Vest4

0.48

MutPred

0.35

Loss of glycosylation at P352 (P = 1e-04);.;Loss of glycosylation at P352 (P = 1e-04);

MVP

0.56

MPC

0.95

ClinPred

0.99

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.52

gMVP

0.19

Mutation Taster

=37/63

disease causing

(source)

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

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chr1-225514759-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over