chr5-74635620-C-T
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
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
NM_003633.4 missense
Scores
2
11
6
Clinical Significance
Conservation
PhyloP100: 6.17
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 -4 ACMG points.
BS2
High AC in GnomAd4 at 6 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ENC1 | NM_003633.4 | c.866G>A | p.Arg289Gln | missense_variant | 2/3 | ENST00000302351.9 | NP_003624.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ENC1 | ENST00000302351.9 | c.866G>A | p.Arg289Gln | missense_variant | 2/3 | 1 | NM_003633.4 | ENSP00000306356.4 | ||
ENC1 | ENST00000618628.4 | c.866G>A | p.Arg289Gln | missense_variant | 3/4 | 5 | ENSP00000479101.1 | |||
ENC1 | ENST00000651128.1 | c.866G>A | p.Arg289Gln | missense_variant | 3/4 | ENSP00000499185.1 | ||||
ENC1 | ENST00000510316.5 | c.647G>A | p.Arg216Gln | missense_variant | 2/3 | 2 | ENSP00000423804.1 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152152Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251338Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135846
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GnomAD4 exome AF: 0.0000157 AC: 23AN: 1461880Hom.: 0 Cov.: 37 AF XY: 0.0000151 AC XY: 11AN XY: 727238
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GnomAD4 genome AF: 0.0000394 AC: 6AN: 152152Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74314
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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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;T;.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
.;D;D;.
M_CAP
Benign
D
MetaRNN
Uncertain
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;.;L
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
N;.;D;N
REVEL
Uncertain
Sift
Uncertain
D;.;D;D
Sift4G
Uncertain
D;D;D;D
Polyphen
B;B;.;B
Vest4
MVP
MPC
ClinPred
D
GERP RS
Varity_R
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at