chr7-102028117-C-G
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP2BS1_SupportingBS2
The NM_181552.4(CUX1):c.161C>G(p.Ala54Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00011 in 1,612,314 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: 𝑓 0.000033 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00012 ( 0 hom. )
Consequence
CUX1
NM_181552.4 missense
NM_181552.4 missense
Scores
2
6
9
Clinical Significance
Conservation
PhyloP100: 5.09
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, CUX1
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.000118 (172/1460138) while in subpopulation NFE AF= 0.000153 (170/1111990). AF 95% confidence interval is 0.000133. There are 0 homozygotes in gnomad4_exome. There are 93 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
BS2
?
High AC in GnomAd at 5 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CUX1 | NM_181552.4 | c.161C>G | p.Ala54Gly | missense_variant | 3/24 | ENST00000292535.12 | |
CUX1 | NM_001913.5 | c.194C>G | p.Ala65Gly | missense_variant | 3/23 | ENST00000622516.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CUX1 | ENST00000292535.12 | c.161C>G | p.Ala54Gly | missense_variant | 3/24 | 1 | NM_181552.4 | A2 | |
CUX1 | ENST00000622516.6 | c.194C>G | p.Ala65Gly | missense_variant | 3/23 | 1 | NM_001913.5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152176Hom.: 0 Cov.: 33
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?
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GnomAD3 exomes AF: 0.0000279 AC: 7AN: 251256Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135788
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GnomAD4 exome AF: 0.000118 AC: 172AN: 1460138Hom.: 0 Cov.: 31 AF XY: 0.000128 AC XY: 93AN XY: 726360
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 26, 2022 | The c.194C>G (p.A65G) alteration is located in exon 3 (coding exon 3) of the CUX1 gene. This alteration results from a C to G substitution at nucleotide position 194, causing the alanine (A) at amino acid position 65 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
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
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D;D;D;D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
N;.;.;N;N;.;D;D;D;D;D;D;D
REVEL
Benign
Sift
Benign
D;.;.;D;D;.;D;T;D;D;D;D;D
Sift4G
Benign
T;.;.;T;T;T;D;T;D;D;D;D;D
Polyphen
D;.;.;P;.;P;D;.;D;D;.;.;.
Vest4
MVP
MPC
0.56
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DG_spliceai
Position offset: -5
Find out detailed SpliceAI scores and Pangolin per-transcript scores at