Variant 7-101816046-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001913.5(CUX1):c.16G>A(p.Gly6Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000209 in 1,433,836 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 29)

Exomes 𝑓: 0.0000016 ( 0 hom. )

Consequence

CUX1
NM_001913.5 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 5.32

Variant links:

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]

CUX1 links:

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;

BP4

Computational evidence support a benign effect (MetaRNN=0.28541607).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CUX1	NM_001913.5 linkuse as main transcript	c.16G>A	p.Gly6Arg	missense_variant	1/23	ENST00000622516.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CUX1	ENST00000622516.6 linkuse as main transcript	c.16G>A	p.Gly6Arg	missense_variant	1/23	1	NM_001913.5		Q13948-1

Frequencies

GnomAD3 genomes

AF:

0.00000675

AC:

AN:

148166

Hom.:

Cov.:

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:

0.0000150

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000156

AC:

AN:

1285670

Hom.:

Cov.:

AF XY:

0.00000156

AC XY:

AN XY:

640050

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.96e-7

Gnomad4 OTH exome

AF:

0.0000205

GnomAD4 genome

AF:

0.00000675

AC:

AN:

148166

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

72208

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:

0.0000150

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CUX1-related disorder

Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 26, 2024

The CUX1 c.16G>A variant is predicted to result in the amino acid substitution p.Gly6Arg. To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.037

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.12

.;.;.;T;.;T;.;.;.

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.47

FATHMM_MKL

Benign

0.59

LIST_S2

Uncertain

0.97

D;D;D;.;D;D;D;D;D

M_CAP

Pathogenic

0.74

MetaRNN

Benign

0.29

T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.4

L;.;.;L;L;L;L;.;.

MutationTaster

Benign

0.70

D;D;D;D;D;D

PROVEAN

Benign

-1.0

N;.;.;N;N;.;N;N;N

REVEL

Benign

0.15

Sift

Benign

0.49

T;.;.;T;T;.;T;T;T

Sift4G

Benign

0.17

T;.;.;T;T;T;T;T;T

Polyphen

0.0040

B;.;.;B;.;B;.;P;.

Vest4

0.30

MutPred

0.38

Gain of MoRF binding (P = 0.0161);Gain of MoRF binding (P = 0.0161);Gain of MoRF binding (P = 0.0161);Gain of MoRF binding (P = 0.0161);Gain of MoRF binding (P = 0.0161);Gain of MoRF binding (P = 0.0161);Gain of MoRF binding (P = 0.0161);Gain of MoRF binding (P = 0.0161);Gain of MoRF binding (P = 0.0161);

MVP

0.068

MPC

0.67

ClinPred

0.45

GERP RS

1.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.0

gMVP

0.42

Splicing

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over