Variant 10-116881536-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001242699.2(ENO4):c.1745T>C(p.Phe582Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000503 in 1,392,698 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000050 ( 0 hom. )

Consequence

ENO4
NM_001242699.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.20

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 made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ENO4	NM_001242699.2 linkuse as main transcript	c.1745T>C	p.Phe582Ser	missense_variant	14/14	ENST00000341276.11
SHTN1	NM_001127211.3 linkuse as main transcript	c.*4808A>G		3_prime_UTR_variant	17/17	ENST00000355371.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ENO4	ENST00000341276.11 linkuse as main transcript	c.1745T>C	p.Phe582Ser	missense_variant	14/14	5	NM_001242699.2	P1	A6NNW6-3
SHTN1	ENST00000355371.9 linkuse as main transcript	c.*4808A>G		3_prime_UTR_variant	17/17	2	NM_001127211.3	P1	A0MZ66-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000139

AC:

AN:

144174

Hom.:

AF XY:

0.0000257

AC XY:

AN XY:

77708

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000973

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000186

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000503

AC:

AN:

1392698

Hom.:

Cov.:

AF XY:

0.00000582

AC XY:

AN XY:

686720

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000280

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000557

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 03, 2023

The c.1745T>C (p.F582S) alteration is located in exon 14 (coding exon 14) of the ENO4 gene. This alteration results from a T to C substitution at nucleotide position 1745, causing the phenylalanine (F) at amino acid position 582 to be replaced by a serine (S). 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

0.27

BayesDel_addAF

Uncertain

0.083

BayesDel_noAF

Uncertain

0.090

Cadd

Benign

Dann

Uncertain

0.98

Eigen

Benign

0.041

Eigen_PC

Benign

0.0031

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.72

T;T;.

M_CAP

Uncertain

0.13

MetaRNN

Uncertain

0.67

D;D;D

MetaSVM

Benign

-0.65

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.57

PROVEAN

Uncertain

-2.6

D;.;.

REVEL

Uncertain

0.43

Sift

Uncertain

0.0020

D;.;.

Sift4G

Uncertain

0.0030

D;D;D

Polyphen

1.0

D;.;.

Vest4

0.64

MutPred

0.59

.;.;Gain of disorder (P = 0.0087);

MVP

0.55

ClinPred

0.49

GERP RS

4.3

Varity_R

0.11

gMVP

0.47

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over