7-101916207-C-G

Position:

• chr7-101916207-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_181552.4(CUX1):​c.123C>G​(p.Phe41Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CUX1 NM_181552.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.32

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CUX1	NM_181552.4	c.123C>G	p.Phe41Leu	missense_variant	2/24	ENST00000292535.12	NP_853530.2
CUX1	NM_001913.5	c.156C>G	p.Phe52Leu	missense_variant	2/23	ENST00000622516.6	NP_001904.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CUX1	ENST00000292535.12	c.123C>G	p.Phe41Leu	missense_variant	2/24	1	NM_181552.4	ENSP00000292535.7
CUX1	ENST00000622516.6	c.156C>G	p.Phe52Leu	missense_variant	2/23	1	NM_001913.5	ENSP00000484760.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Jan 29, 2024

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.14
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.44	.;.;.;T;T;.;.;.;D;D;.;.;.
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.91	D;D;D;.;D;D;D;D;.;D;D;D;D
M_CAP	Benign	0.020	T
MetaRNN	Uncertain	0.54	D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.59	T
MutationAssessor	Uncertain	2.3	.;.;.;.;.;.;.;.;M;M;M;M;M
PrimateAI	Pathogenic	0.88	D
PROVEAN	Uncertain	-3.7	D;.;.;D;.;D;D;D;D;D;D;D;D
REVEL	Benign	0.28
Sift	Uncertain	0.0040	D;.;.;D;.;D;D;D;D;D;D;D;D
Sift4G	Benign	0.55	T;.;.;T;T;T;D;T;D;D;D;D;D
Polyphen		0.99	D;.;.;B;B;.;D;.;D;D;.;.;.
Vest4		0.95
MutPred		0.25		.;.;.;.;.;.;.;.;Gain of ubiquitination at K43 (P = 0.0702);Gain of ubiquitination at K43 (P = 0.0702);Gain of ubiquitination at K43 (P = 0.0702);Gain of ubiquitination at K43 (P = 0.0702);Gain of ubiquitination at K43 (P = 0.0702);
MVP		0.69
MPC		0.65
ClinPred		0.98	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.33
gMVP		0.97

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: chr7-101559487;