rs755928199

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000372090.6(TOE1):​c.-27C>A variant causes a 5 prime UTR 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Consequence

TOE1
ENST00000372090.6 5_prime_UTR

Scores

1
18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.382
Variant links:
Genes affected
MUTYH (HGNC:7527): (mutY DNA glycosylase) This gene encodes a DNA glycosylase involved in oxidative DNA damage repair. The enzyme excises adenine bases from the DNA backbone at sites where adenine is inappropriately paired with guanine, cytosine, or 8-oxo-7,8-dihydroguanine, a major oxidatively damaged DNA lesion. The protein is localized to the nucleus and mitochondria. This gene product is thought to play a role in signaling apoptosis by the introduction of single-strand breaks following oxidative damage. Mutations in this gene result in heritable predisposition to colorectal cancer, termed MUTYH-associated polyposis (MAP). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2017]
TOE1 (HGNC:15954): (target of EGR1, exonuclease) Enables poly(A)-specific ribonuclease activity and snRNA binding activity. Involved in RNA phosphodiester bond hydrolysis, exonucleolytic and snRNA 3'-end processing. Located in Cajal body and cytoplasm. Implicated in pontocerebellar hypoplasia type 7. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.061538875).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MUTYHNM_001128425.2 linkuse as main transcriptc.29G>T p.Arg10Leu missense_variant 1/16 ENST00000710952.2 NP_001121897.1
TOE1NM_025077.4 linkuse as main transcriptc.-27C>A 5_prime_UTR_variant 1/8 ENST00000372090.6 NP_079353.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MUTYHENST00000710952.2 linkuse as main transcriptc.29G>T p.Arg10Leu missense_variant 1/16 NM_001128425.2 ENSP00000518552
TOE1ENST00000372090.6 linkuse as main transcriptc.-27C>A 5_prime_UTR_variant 1/81 NM_025077.4 ENSP00000361162 P1Q96GM8-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.099
BayesDel_addAF
Benign
-0.27
T
BayesDel_noAF
Benign
-0.63
CADD
Benign
9.3
DANN
Benign
0.92
DEOGEN2
Benign
0.039
T;.;.;.;.
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.055
N
LIST_S2
Benign
0.51
T;T;T;T;T
M_CAP
Benign
0.0029
T
MetaRNN
Benign
0.062
T;T;T;T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
0.90
L;L;L;.;.
MutationTaster
Benign
1.0
N;N;N;N;N;N;N;N
PrimateAI
Benign
0.26
T
PROVEAN
Benign
-0.090
N;N;N;N;N
REVEL
Benign
0.033
Sift
Uncertain
0.025
D;D;D;D;T
Sift4G
Benign
0.21
T;T;T;T;T
Polyphen
0.0
B;B;.;B;.
Vest4
0.094
MutPred
0.33
Loss of disorder (P = 0.0137);Loss of disorder (P = 0.0137);Loss of disorder (P = 0.0137);Loss of disorder (P = 0.0137);Loss of disorder (P = 0.0137);
MVP
0.30
MPC
0.14
ClinPred
0.21
T
GERP RS
0.47
Varity_R
0.074
gMVP
0.33

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.12
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: rs755928199; hg19: chr1-45805898; API