chr7-101916207-C-G

Position:

• chr7-101916207-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP2

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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CUX1 NM_181552.4 missense
• Clinical Significance: Not reported in ClinVar
• 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 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	c.123C>G	p.Phe41Leu	missense_variant	2/24	ENST00000292535.12
CUX1	NM_001913.5	c.156C>G	p.Phe52Leu	missense_variant	2/23	ENST00000622516.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CUX1	ENST00000292535.12	c.123C>G	p.Phe41Leu	missense_variant	2/24	1	NM_181552.4	A2
CUX1	ENST00000622516.6	c.156C>G	p.Phe52Leu	missense_variant	2/23	1	NM_001913.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

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
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;D;D;D;D;D
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;