NM_181552.4:c.190A>G

Variant names:

• chr7-102070339-A-G
• NM_181552.4:c.190A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_181552.4(CUX1):​c.190A>G​(p.Ile64Val) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CUX1 NM_181552.4 missense, splice_region
• Scores: Splicing: ADA: 0.002262
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.83

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2169537).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CUX1	NM_181552.4	c.190A>G	p.Ile64Val	missense_variant, splice_region_variant	Exon 4 of 24	ENST00000292535.12	NP_853530.2
CUX1	NM_001913.5	c.223A>G	p.Ile75Val	missense_variant, splice_region_variant	Exon 4 of 23	ENST00000622516.6	NP_001904.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CUX1	ENST00000292535.12	c.190A>G	p.Ile64Val	missense_variant, splice_region_variant	Exon 4 of 24	1	NM_181552.4	ENSP00000292535.7
CUX1	ENST00000622516.6	c.223A>G	p.Ile75Val	missense_variant, splice_region_variant	Exon 4 of 23	1	NM_001913.5	ENSP00000484760.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

May 26, 2023

GeneDx

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter 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	Uncertain	0.42
BayesDel_addAF	Benign	-0.027	T
BayesDel_noAF	Benign	-0.28
CADD	Uncertain	25
DANN	Benign	0.97
DEOGEN2	Benign	0.11	.;.;.;T;.;T;.;.;.;T;T;.;.;.
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.91	D;D;T;.;D;D;T;D;D;.;D;D;D;T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.22	T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.3	.;.;.;.;.;.;.;.;.;L;L;L;L;L
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.35	N;.;.;N;N;.;N;N;N;N;N;N;N;N
REVEL	Benign	0.15
Sift	Benign	0.27	T;.;.;T;T;.;T;T;T;T;T;T;T;T
Sift4G	Benign	0.61	T;.;.;T;T;T;T;T;T;T;T;T;T;T
Polyphen		0.76	P;.;.;P;.;P;.;D;.;D;D;.;.;.
Vest4		0.33
MutPred		0.20		.;.;.;.;.;.;.;.;.;Gain of disorder (P = 0.162);Gain of disorder (P = 0.162);Gain of disorder (P = 0.162);Gain of disorder (P = 0.162);Gain of disorder (P = 0.162);
MVP		0.13
MPC		0.46
ClinPred		0.65	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.23
gMVP		0.79

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0023
dbscSNV1_RF	Benign	0.012
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: chr7-101713619;