chr7-102028120-C-G

Variant names:

• chr7-102028120-C-G
• NM_181552.4:c.164C>G

Variant summary

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

The NM_181552.4(CUX1):​c.164C>G​(p.Pro55Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,172 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CUX1 NM_181552.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.09

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CUX1	NM_181552.4	c.164C>G	p.Pro55Arg	missense_variant	Exon 3 of 24	ENST00000292535.12	NP_853530.2
CUX1	NM_001913.5	c.197C>G	p.Pro66Arg	missense_variant	Exon 3 of 23	ENST00000622516.6	NP_001904.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CUX1	ENST00000292535.12	c.164C>G	p.Pro55Arg	missense_variant	Exon 3 of 24	1	NM_181552.4	ENSP00000292535.7
CUX1	ENST00000622516.6	c.197C>G	p.Pro66Arg	missense_variant	Exon 3 of 23	1	NM_001913.5	ENSP00000484760.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460172 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726366

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Uncertain	0.13
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.36	.;.;.;T;.;T;.;.;D;D;.;.;.
Eigen	Pathogenic	0.70
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.97	D;D;D;.;D;D;D;D;.;D;D;D;D
M_CAP	Benign	0.044	D
MetaRNN	Uncertain	0.61	D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.48	T
MutationAssessor	Uncertain	2.4	.;.;.;.;.;.;.;.;M;M;M;M;M
PrimateAI	Pathogenic	0.84	D
PROVEAN	Pathogenic	-6.2	D;.;.;D;D;.;D;D;D;D;D;D;D
REVEL	Benign	0.27
Sift	Pathogenic	0.0	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		1.0	D;.;.;D;.;D;D;.;D;D;.;.;.
Vest4		0.83
MutPred		0.28		.;.;.;.;.;.;.;.;Gain of MoRF binding (P = 4e-04);Gain of MoRF binding (P = 4e-04);Gain of MoRF binding (P = 4e-04);Gain of MoRF binding (P = 4e-04);Gain of MoRF binding (P = 4e-04);
MVP		0.55
MPC		0.59
ClinPred		0.96	D
GERP RS		5.6
Varity_R		0.50
gMVP		0.82

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: chr7-101671400;