Genetic Variant ENO4:p.Leu596Phe (chr10-116881577-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001242699.2(ENO4):c.1786C>T(p.Leu596Phe) 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. 16/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 33)

Failed GnomAD Quality Control

Consequence

ENO4
NM_001242699.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.109

Publications

0 publications found

Variant links:

Genes affected

ENO4 (HGNC:31670): (enolase 4) Predicted to enable phosphopyruvate hydratase activity. Predicted to be involved in glycolytic process and regulation of vacuole fusion, non-autophagic. Predicted to act upstream of or within cilium organization and flagellated sperm motility. Predicted to be located in sperm principal piece. Predicted to be part of phosphopyruvate hydratase complex. [provided by Alliance of Genome Resources, Apr 2022]

ENO4 links:

SHTN1 (HGNC:29319): (shootin 1) Enables identical protein binding activity. Involved in positive regulation of neuron migration. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

SHTN1 links:

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ACMG classification

Classification was made for transcript

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=0.07523951).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001242699.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ENO4	NM_001242699.2	MANE Select	c.1786C>T	p.Leu596Phe	missense	Exon 14 of 14	NP_001229628.1	A6NNW6-3
SHTN1	NM_001127211.3	MANE Select	c.*4767G>A		3_prime_UTR	Exon 17 of 17	NP_001120683.1	A0MZ66-1
SHTN1	NM_001258298.2		c.*4767G>A		3_prime_UTR	Exon 16 of 16	NP_001245227.1	A0MZ66-5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ENO4	ENST00000341276.11	TSL:5 MANE Select	c.1786C>T	p.Leu596Phe	missense	Exon 14 of 14	ENSP00000345555.6	A6NNW6-3
ENO4	ENST00000409522.5	TSL:1	c.835C>T	p.Leu279Phe	missense	Exon 7 of 7	ENSP00000387194.1	A6NNW6-2
SHTN1	ENST00000355371.9	TSL:2 MANE Select	c.*4767G>A		3_prime_UTR	Exon 17 of 17	ENSP00000347532.4	A0MZ66-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

152190

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

152190

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74344

African (AFR)

AF:

0.00

AC:

AN:

41460

American (AMR)

AF:

0.00

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68030

Other (OTH)

AF:

0.00

AC:

AN:

2092

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.52

CADD

Benign

0.99

(source)

DANN

Benign

0.56

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.63

M_CAP

Benign

0.048

MetaRNN

Benign

0.075

MetaSVM

Benign

-0.96

PhyloP100

0.11

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.35

REVEL

Benign

0.088

Sift

Benign

0.48

Sift4G

Benign

0.71

Polyphen

0.73

Vest4

0.10

MVP

0.16

ClinPred

0.16

GERP RS

2.5

Varity_R

0.030

gMVP

0.13

Mutation Taster

=96/4

polymorphism

(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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over