Genetic Variant CCNQ:c.430-13C>T (chrX-153592746-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_152274.5(CCNQ):c.430-13C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000126 in 1,191,863 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 5 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 2 hem., cov: 25)

Exomes 𝑓: 0.000011 ( 0 hom. 3 hem. )

Consequence

CCNQ
NM_152274.5 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.930

Variant links:

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]

CCNQ links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant X-153592746-G-A is Benign according to our data. Variant chrX-153592746-G-A is described in ClinVar as [Benign]. Clinvar id is 1938403.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CCNQ	NM_152274.5 link	c.430-13C>T	intron_variant	Intron 3 of 4	ENST00000576892.8	NP_689487.2	Q8N1B3-1
CCNQ	NM_001130997.3 link	c.430-13C>T	intron_variant	Intron 3 of 4		NP_001124469.1	Q8N1B3-2
CCNQ	XM_011531214.3 link	c.304-13C>T	intron_variant	Intron 3 of 4		XP_011529516.1
CCNQ	XM_047442631.1 link	c.429+1801C>T	intron_variant	Intron 3 of 3		XP_047298587.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCNQ	ENST00000576892.8 link	c.430-13C>T		intron_variant	Intron 3 of 4	1	NM_152274.5	ENSP00000461135.1		Q8N1B3-1

Frequencies

GnomAD3 genomes

AF:

0.0000266

AC:

AN:

112934

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000560

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00418

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000562

AC:

AN:

160159

AF XY:

0.0000197

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000715

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000111

AC:

AN:

1078876

Hom.:

Cov.:

AF XY:

0.00000866

AC XY:

AN XY:

346250

show subpopulations

African (AFR)

AF:

0.000153

AC:

AN:

26068

American (AMR)

AF:

0.00

AC:

AN:

34094

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19146

East Asian (EAS)

AF:

0.000201

AC:

AN:

29784

South Asian (SAS)

AF:

0.00

AC:

AN:

52280

European-Finnish (FIN)

AF:

0.0000252

AC:

AN:

39752

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4090

European-Non Finnish (NFE)

AF:

0.00000121

AC:

AN:

828232

Other (OTH)

AF:

0.00

AC:

AN:

45430

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000266

AC:

AN:

112987

Hom.:

Cov.:

AF XY:

0.0000569

AC XY:

AN XY:

35139

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31195

American (AMR)

AF:

0.00

AC:

AN:

10802

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2654

East Asian (EAS)

AF:

0.000562

AC:

AN:

3560

South Asian (SAS)

AF:

0.00

AC:

AN:

2769

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6261

Middle Eastern (MID)

AF:

0.00459

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53293

Other (OTH)

AF:

0.00

AC:

AN:

1549

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000264

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 28, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.017

(source)

DANN

Benign

0.75

PhyloP100

-0.93

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

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X-153592746-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over