Variant 5-74635620-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP2BS2

The NM_003633.4(ENC1):c.866G>A(p.Arg289Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000018 in 1,614,032 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

ENC1
NM_003633.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.17

Variant links:

Genes affected

ENC1 (HGNC:3345): (ectodermal-neural cortex 1) This gene encodes a member of the kelch-related family of actin-binding proteins. The encoded protein plays a role in the oxidative stress response as a regulator of the transcription factor Nrf2, and expression of this gene may play a role in malignant transformation. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Feb 2012]

ENC1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PP2

Missense variant where missense usually causes diseases, ENC1

BS2

High AC in GnomAd4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ENC1	NM_003633.4 linkuse as main transcript	c.866G>A	p.Arg289Gln	missense_variant	2/3	ENST00000302351.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ENC1	ENST00000302351.9 linkuse as main transcript	c.866G>A	p.Arg289Gln	missense_variant	2/3	1	NM_003633.4	P1	O14682-1
ENC1	ENST00000618628.4 linkuse as main transcript	c.866G>A	p.Arg289Gln	missense_variant	3/4	5		P1	O14682-1
ENC1	ENST00000651128.1 linkuse as main transcript	c.866G>A	p.Arg289Gln	missense_variant	3/4			P1	O14682-1
ENC1	ENST00000510316.5 linkuse as main transcript	c.647G>A	p.Arg216Gln	missense_variant	2/3	2			O14682-2

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

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:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251338

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135846

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000157

AC:

AN:

1461880

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000171

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152152

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000644

Hom.:

Bravo

AF:

0.0000491

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

Apr 13, 2023

The c.866G>A (p.R289Q) alteration is located in exon 2 (coding exon 1) of the ENC1 gene. This alteration results from a G to A substitution at nucleotide position 866, causing the arginine (R) at amino acid position 289 to be replaced by a glutamine (Q). 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

0.15

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Uncertain

-0.060

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.22

T;T;.;T

Eigen

Uncertain

0.33

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Uncertain

0.95

M_CAP

Benign

0.032

MetaRNN

Uncertain

0.47

T;T;T;T

MetaSVM

Benign

-0.55

MutationAssessor

Benign

1.9

L;L;.;L

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.88

PROVEAN

Uncertain

-2.5

N;.;D;N

REVEL

Uncertain

0.44

Sift

Uncertain

0.0040

D;.;D;D

Sift4G

Uncertain

0.012

D;D;D;D

Polyphen

0.30

B;B;.;B

Vest4

0.61

MVP

0.74

MPC

1.0

ClinPred

0.64

GERP RS

6.0

Varity_R

0.36

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