7-102104386-C-G

Position:

• chr7-102104386-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_181552.4(CUX1):​c.457C>G​(p.Leu153Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: CUX1 NM_181552.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.09

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]

ACMG classification

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=0.14333934).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CUX1	NM_181552.4	c.457C>G	p.Leu153Val	missense_variant	6/24	ENST00000292535.12
CUX1	NM_001913.5	c.490C>G	p.Leu164Val	missense_variant	6/23	ENST00000622516.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CUX1	ENST00000292535.12	c.457C>G	p.Leu153Val	missense_variant	6/24	1	NM_181552.4	A2
CUX1	ENST00000622516.6	c.490C>G	p.Leu164Val	missense_variant	6/23	1	NM_001913.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Global developmental delay with or without impaired intellectual development Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein

Sep 28, 2022

ACMG classification criteria: PM2 moderated, PP2 supporting, BP4 supporting -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Uncertain	0.050	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	24
DANN	Uncertain	0.99
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.074
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.92	D;D;D;.;D;D;D;D;D;.;D;D;D;D
M_CAP	Benign	0.040	D
MetaRNN	Benign	0.14	T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.40	T
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;D;D;D;D;D;D
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.95	N;.;.;N;N;.;N;N;N;N;N;N;N;N
REVEL	Benign	0.11
Sift	Benign	0.60	T;.;.;T;T;.;T;T;D;T;T;T;T;T
Sift4G	Benign	0.35	T;.;.;T;T;T;T;T;T;T;T;T;T;T
Polyphen		0.59	P;.;.;B;.;B;.;B;.;B;B;.;.;.
Vest4		0.35
MutPred		0.13		.;.;.;.;.;.;.;.;.;Gain of methylation at K154 (P = 0.0308);Gain of methylation at K154 (P = 0.0308);Gain of methylation at K154 (P = 0.0308);Gain of methylation at K154 (P = 0.0308);Gain of methylation at K154 (P = 0.0308);
MVP		0.49
MPC		0.56
ClinPred		0.29	T
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.23
gMVP		0.85

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.

Other links and lift over

hg19: chr7-101747666;