chrX-153588415-T-C

Variant names:

• chrX-153588415-T-C
• NM_152274.5:c.697A>G

Variant summary

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

The NM_152274.5(CCNQ):​c.697A>G​(p.Ile233Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000912 in 1,096,814 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 9/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: CCNQ NM_152274.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.49

Genes affected

CCNQ (HGNC:28434): (cyclin Q) Mutations in this gene have been shown to cause an X-linked dominant STAR syndrome that typically manifests syndactyly, telecanthus and anogenital and renal malformations. The protein encoded by this gene contains a cyclin-box-fold domain which suggests it may have a role in controlling nuclear cell division cycles. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Oct 2008]

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=0.22514671).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCNQ	NM_152274.5	c.697A>G	p.Ile233Val	missense_variant	Exon 5 of 5	ENST00000576892.8	NP_689487.2
CCNQ	XM_011531214.3	c.571A>G	p.Ile191Val	missense_variant	Exon 5 of 5		XP_011529516.1
CCNQ	XM_047442631.1	c.469A>G	p.Ile157Val	missense_variant	Exon 4 of 4		XP_047298587.1
CCNQ	NM_001130997.3	c.658-21A>G		intron_variant	Intron 4 of 4		NP_001124469.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCNQ	ENST00000576892.8	c.697A>G	p.Ile233Val	missense_variant	Exon 5 of 5	1	NM_152274.5	ENSP00000461135.1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome AF: 9.12e-7 AC: 1 AN: 1096814 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 362230

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: 0.00000119

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 24

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Oct 07, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 233 of the CCNQ protein (p.Ile233Val). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CCNQ-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.024	T
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.78	T
PrimateAI	Uncertain	0.54	T
Sift4G	Benign	0.24	T
Polyphen		0.43	B
Vest4		0.16
MutPred		0.57		Loss of catalytic residue at V234 (P = 0.2271);
MVP		0.65
ClinPred		0.66	D
GERP RS		4.4
Varity_R		0.17

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chrX-152853873;