X-153588390-T-C

Position:

• chrX-153588390-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM2 PP3_Moderate BP6_Moderate

The NM_152274.5(CCNQ):​c.722A>G​(p.Tyr241Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 26)
• Consequence: CCNQ NM_152274.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.10

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.848
• BP6: Variant X-153588390-T-C is Benign according to our data. Variant chrX-153588390-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3053647.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCNQ	NM_152274.5	c.722A>G	p.Tyr241Cys	missense_variant	5/5	ENST00000576892.8
CCNQ	NM_001130997.3	c.662A>G	p.Tyr221Cys	missense_variant	5/5
CCNQ	XM_011531214.3	c.596A>G	p.Tyr199Cys	missense_variant	5/5
CCNQ	XM_047442631.1	c.494A>G	p.Tyr165Cys	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCNQ	ENST00000576892.8	c.722A>G	p.Tyr241Cys	missense_variant	5/5	1	NM_152274.5	P1

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 26

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

CCNQ-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 02, 2024

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.80
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.22
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.34	T;.
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.87	D;T
M_CAP	Uncertain	0.22	D
MetaRNN	Pathogenic	0.85	D;D
MetaSVM	Uncertain	-0.14	T
MutationTaster	Benign	1.0	D
PrimateAI	Pathogenic	0.79	T
Sift4G	Uncertain	0.0020	D;D
Polyphen		1.0	D;D
Vest4		0.81
MutPred		0.67		Loss of catalytic residue at I240 (P = 0.061);.;
MVP		1.0
ClinPred		0.98	D
GERP RS		4.4
Varity_R		0.70

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: chrX-152853848;