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GeneBe

5-74636280-C-T

Variant summary

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

The NM_003633.4(ENC1):​c.206G>A​(p.Arg69His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,614,166 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

ENC1
NM_003633.4 missense

Scores

3
7
8

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.91
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]

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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 GnomAdExome4 at 19 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ENC1NM_003633.4 linkuse as main transcriptc.206G>A p.Arg69His missense_variant 2/3 ENST00000302351.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ENC1ENST00000302351.9 linkuse as main transcriptc.206G>A p.Arg69His missense_variant 2/31 NM_003633.4 P1O14682-1
ENC1ENST00000618628.4 linkuse as main transcriptc.206G>A p.Arg69His missense_variant 3/45 P1O14682-1
ENC1ENST00000651128.1 linkuse as main transcriptc.206G>A p.Arg69His missense_variant 3/4 P1O14682-1
ENC1ENST00000510316.5 linkuse as main transcriptc.-14G>A 5_prime_UTR_variant 2/32 O14682-2

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152156
Hom.:
0
Cov.:
32
show subpopulations
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251448
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135904
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:
0.00000879
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000130
AC:
19
AN:
1461892
Hom.:
0
Cov.:
37
AF XY:
0.00000963
AC XY:
7
AN XY:
727246
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000135
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152274
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74440
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000540
Hom.:
0
Bravo
AF:
0.0000151
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.15
BayesDel_addAF
Pathogenic
0.18
D
BayesDel_noAF
Uncertain
0.030
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.18
T;T;T
Eigen
Uncertain
0.21
Eigen_PC
Uncertain
0.40
FATHMM_MKL
Pathogenic
0.97
D
M_CAP
Benign
0.038
D
MetaRNN
Uncertain
0.66
D;D;D
MetaSVM
Benign
-0.73
T
MutationAssessor
Benign
0.025
N;N;N
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Pathogenic
0.86
D
PROVEAN
Benign
-0.65
N;.;N
REVEL
Uncertain
0.31
Sift
Uncertain
0.0010
D;.;D
Sift4G
Benign
0.13
T;T;T
Polyphen
0.31
B;B;B
Vest4
0.73
MutPred
0.59
Loss of helix (P = 0.2022);Loss of helix (P = 0.2022);Loss of helix (P = 0.2022);
MVP
0.79
MPC
1.1
ClinPred
0.53
D
GERP RS
5.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.39

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.

Other links and lift over

dbSNP: rs775660875; hg19: chr5-73932105; API