chr7-102104408-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate
The NM_181552.4(CUX1):c.479T>C(p.Ile160Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,200 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
CUX1
NM_181552.4 missense
NM_181552.4 missense
Scores
1
6
10
Clinical Significance
Conservation
PhyloP100: 7.73
Genes affected
CUX1 (HGNC:2557): (cut like homeobox 1) The protein encoded by this gene is a member of the homeodomain family of DNA binding proteins. It may regulate gene expression, morphogenesis, and differentiation and it may also play a role in the cell cycle progession. Several alternatively spliced transcript variants encoding different isoforms have been identified.[provided by RefSeq, Feb 2011]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP2
?
Missense variant where missense usually causes diseases, CUX1
BP4
?
Computational evidence support a benign effect (MetaRNN=0.20903313).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CUX1 | NM_181552.4 | c.479T>C | p.Ile160Thr | missense_variant | 6/24 | ENST00000292535.12 | |
CUX1 | NM_001913.5 | c.512T>C | p.Ile171Thr | missense_variant | 6/23 | ENST00000622516.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CUX1 | ENST00000292535.12 | c.479T>C | p.Ile160Thr | missense_variant | 6/24 | 1 | NM_181552.4 | A2 | |
CUX1 | ENST00000622516.6 | c.512T>C | p.Ile171Thr | missense_variant | 6/23 | 1 | NM_001913.5 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 genomes
?
Cov.:
31
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250696Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135542
GnomAD3 exomes
AF:
AC:
1
AN:
250696
Hom.:
AF XY:
AC XY:
1
AN XY:
135542
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1460200Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1AN XY: 726482
GnomAD4 exome
AF:
AC:
2
AN:
1460200
Hom.:
Cov.:
33
AF XY:
AC XY:
1
AN XY:
726482
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? Cov.: 31
GnomAD4 genome
?
Cov.:
31
Alfa
AF:
Hom.:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 28, 2023 | The c.512T>C (p.I171T) alteration is located in exon 6 (coding exon 6) of the CUX1 gene. This alteration results from a T to C substitution at nucleotide position 512, causing the isoleucine (I) at amino acid position 171 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 17, 2023 | This variant has not been reported in the literature in individuals affected with CUX1-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CUX1 protein function. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 171 of the CUX1 protein (p.Ile171Thr). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;.;D;D;D;D;D;.;D;D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D;D;D;D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.;.;N;N;.;N;N;N;N;N;N;N;N
REVEL
Benign
Sift
Benign
T;.;.;T;T;.;T;T;D;T;T;T;T;T
Sift4G
Benign
T;.;.;T;T;T;T;T;T;T;T;T;T;T
Polyphen
B;.;.;B;.;B;.;P;.;P;P;.;.;.
Vest4
MutPred
0.16
.;.;.;.;.;.;.;.;.;Loss of methylation at K164 (P = 0.0845);Loss of methylation at K164 (P = 0.0845);Loss of methylation at K164 (P = 0.0845);Loss of methylation at K164 (P = 0.0845);Loss of methylation at K164 (P = 0.0845);
MVP
MPC
0.70
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at