Variant 7-102097370-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate

The NM_181552.4(CUX1):c.275T>C(p.Val92Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,455,716 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CUX1
NM_181552.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.49

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 1 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.

BP4

Computational evidence support a benign effect (MetaRNN=0.17059499).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CUX1	NM_181552.4 linkuse as main transcript	c.275T>C	p.Val92Ala	missense_variant	5/24	ENST00000292535.12
CUX1	NM_001913.5 linkuse as main transcript	c.308T>C	p.Val103Ala	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.275T>C	p.Val92Ala	missense_variant	5/24	1	NM_181552.4	A2	P39880-1
CUX1	ENST00000622516.6 linkuse as main transcript	c.308T>C	p.Val103Ala	missense_variant	5/23	1	NM_001913.5		Q13948-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000409

AC:

AN:

244626

Hom.:

AF XY:

0.00

AC XY:

AN XY:

132308

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000347

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1455716

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

724206

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:

0.0000118

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

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

Baylor Genetics

Feb 06, 2020

This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.31

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.13

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

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.011

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.76

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

M_CAP

Benign

0.016

MetaRNN

Benign

0.17

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

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

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

MutationTaster

Benign

1.0

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

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-2.0

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

REVEL

Benign

0.13

Sift

Benign

0.040

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

Sift4G

Benign

0.50

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

Polyphen

0.17

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

Vest4

0.54

MutPred

0.28

.;.;.;.;.;.;.;.;Gain of disorder (P = 0.0796);Gain of disorder (P = 0.0796);Gain of disorder (P = 0.0796);Gain of disorder (P = 0.0796);Gain of disorder (P = 0.0796);

MVP

0.11

MPC

0.67

ClinPred

0.32

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.037

gMVP

0.78

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

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