X-153592536-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_152274.5(CCNQ):c.627C>T(p.Ala209Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00197 in 1,211,231 control chromosomes in the GnomAD database, including 17 homozygotes. There are 1,171 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0012 ( 1 hom., 57 hem., cov: 25)

Exomes 𝑓: 0.0021 ( 16 hom. 1114 hem. )

Consequence

CCNQ
NM_152274.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.442

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant X-153592536-G-A is Benign according to our data. Variant chrX-153592536-G-A is described in ClinVar as [Benign]. Clinvar id is 702552.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-153592536-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-0.442 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0012 (136/113391) while in subpopulation SAS AF = 0.0243 (68/2797). AF 95% confidence interval is 0.0197. There are 1 homozygotes in GnomAd4. There are 57 alleles in the male GnomAd4 subpopulation. Median coverage is 25. This position FAILED quality control check.

BS2

High Hemizygotes in GnomAd4 at 57 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCNQ	NM_152274.5 link	c.627C>T	p.Ala209Ala	synonymous_variant	Exon 4 of 5	ENST00000576892.8	NP_689487.2	Q8N1B3-1
CCNQ	NM_001130997.3 link	c.627C>T	p.Ala209Ala	synonymous_variant	Exon 4 of 5		NP_001124469.1	Q8N1B3-2
CCNQ	XM_011531214.3 link	c.501C>T	p.Ala167Ala	synonymous_variant	Exon 4 of 5		XP_011529516.1
CCNQ	XM_047442631.1 link	c.429+2011C>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.627C>T	p.Ala209Ala	synonymous_variant	Exon 4 of 5	1	NM_152274.5	ENSP00000461135.1		Q8N1B3-1

Frequencies

GnomAD3 genomes

AF:

0.00120

AC:

136

AN:

113337

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000375

Gnomad EAS

AF:

0.000279

Gnomad SAS

AF:

0.0243

Gnomad FIN

AF:

0.000157

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00120

Gnomad OTH

AF:

0.000655

GnomAD2 exomes

AF:

0.00321

AC:

580

AN:

180830

AF XY:

0.00535

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000731

Gnomad ASJ exome

AF:

0.000539

Gnomad EAS exome

AF:

0.000145

Gnomad FIN exome

AF:

0.000127

Gnomad NFE exome

AF:

0.000999

Gnomad OTH exome

AF:

0.00247

GnomAD4 exome

AF:

0.00205

AC:

2255

AN:

1097840

Hom.:

Cov.:

AF XY:

0.00307

AC XY:

1114

AN XY:

363286

show subpopulations

Gnomad4 AFR exome

AF:

0.000114

AC:

AN:

26395

Gnomad4 AMR exome

AF:

0.0000568

AC:

AN:

35193

Gnomad4 ASJ exome

AF:

0.000206

AC:

AN:

19382

Gnomad4 EAS exome

AF:

0.0000662

AC:

AN:

30201

Gnomad4 SAS exome

AF:

0.0275

AC:

1487

AN:

54111

Gnomad4 FIN exome

AF:

0.000198

AC:

AN:

40376

Gnomad4 NFE exome

AF:

0.000745

AC:

627

AN:

841991

Gnomad4 Remaining exome

AF:

0.00193

AC:

AN:

46062

Heterozygous variant carriers

132

198

264

330

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

114

152

190

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00120

AC:

136

AN:

113391

Hom.:

Cov.:

AF XY:

0.00160

AC XY:

AN XY:

35537

show subpopulations

Gnomad4 AFR

AF:

0.00

AC:

AN:

Gnomad4 AMR

AF:

0.00

AC:

AN:

Gnomad4 ASJ

AF:

0.000375

AC:

0.000375235

AN:

0.000375235

Gnomad4 EAS

AF:

0.000280

AC:

0.00027972

AN:

0.00027972

Gnomad4 SAS

AF:

0.0243

AC:

0.0243118

AN:

0.0243118

Gnomad4 FIN

AF:

0.000157

AC:

0.000157183

AN:

0.000157183

Gnomad4 NFE

AF:

0.00120

AC:

0.00119945

AN:

0.00119945

Gnomad4 OTH

AF:

0.000647

AC:

0.000646831

AN:

0.000646831

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000873

Hom.:

Bravo

AF:

0.000710

EpiCase

AF:

0.00153

EpiControl

AF:

0.000831

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:5

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Oct 26, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.34

DANN

Benign

0.56

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over