Variant 7-102097381-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2

The NM_181552.4(CUX1):c.286G>C(p.Asp96His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,456,296 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

CUX1
NM_181552.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.07

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), CUX1. . Gene score misZ 3.7492 (greater than the threshold 3.09). Trascript score misZ 3.103 (greater than threshold 3.09). GenCC has associacion of gene with global developmental delay with or without impaired intellectual development, autosomal dominant non-syndromic intellectual disability.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CUX1	NM_181552.4 linkuse as main transcript	c.286G>C	p.Asp96His	missense_variant	5/24	ENST00000292535.12
CUX1	NM_001913.5 linkuse as main transcript	c.319G>C	p.Asp107His	missense_variant	5/23	ENST00000622516.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CUX1	ENST00000292535.12 linkuse as main transcript	c.286G>C	p.Asp96His	missense_variant	5/24	1	NM_181552.4	A2	P39880-1
CUX1	ENST00000622516.6 linkuse as main transcript	c.319G>C	p.Asp107His	missense_variant	5/23	1	NM_001913.5		Q13948-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1456296

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724450

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:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Global developmental delay with or without impaired intellectual development

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center

Sep 22, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.74

BayesDel_addAF

Uncertain

0.10

BayesDel_noAF

Benign

-0.090

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.19

.;.;.;T;.;T;.;.;D;D;.;.;.

Eigen

Uncertain

0.65

Eigen_PC

Pathogenic

0.74

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.97

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

M_CAP

Benign

0.027

MetaRNN

Uncertain

0.47

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

MetaSVM

Benign

-0.83

MutationAssessor

Benign

1.7

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

MutationTaster

Benign

1.0

D;D;D;D;D;D;D;D;D;D;D;D;D

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-2.4

N;.;.;N;N;.;D;D;D;D;D;D;D

REVEL

Benign

0.27

Sift

Uncertain

0.021

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

Sift4G

Benign

0.090

T;.;.;T;T;T;D;D;D;D;D;D;D

Polyphen

0.62

P;.;.;P;.;P;.;D;D;D;.;.;.

Vest4

0.56

MutPred

0.32

.;.;.;.;.;.;.;.;Loss of loop (P = 0.1242);Loss of loop (P = 0.1242);Loss of loop (P = 0.1242);Loss of loop (P = 0.1242);Loss of loop (P = 0.1242);

MVP

0.17

MPC

0.66

ClinPred

0.83

GERP RS

6.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.34

gMVP

0.80

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over