Variant X-153588388-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_152274.5(CCNQ):c.724A>G(p.Thr242Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00277 in 1,208,786 control chromosomes in the GnomAD database, including 7 homozygotes. There are 1,036 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 11/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0020 ( 1 hom., 54 hem., cov: 25)

Exomes 𝑓: 0.0029 ( 6 hom. 982 hem. )

Consequence

CCNQ
NM_152274.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:3

Conservation

PhyloP100: 1.26

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 made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01023373).

BP6

Variant X-153588388-T-C is Benign according to our data. Variant chrX-153588388-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 702042.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-153588388-T-C is described in Lovd as [Likely_benign].

BS2

High Hemizygotes in GnomAd4 at 54 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CCNQ	NM_152274.5 linkuse as main transcript	c.724A>G	p.Thr242Ala	missense_variant	5/5	ENST00000576892.8
CCNQ	NM_001130997.3 linkuse as main transcript	c.664A>G	p.Thr222Ala	missense_variant	5/5
CCNQ	XM_011531214.3 linkuse as main transcript	c.598A>G	p.Thr200Ala	missense_variant	5/5
CCNQ	XM_047442631.1 linkuse as main transcript	c.496A>G	p.Thr166Ala	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCNQ	ENST00000576892.8 linkuse as main transcript	c.724A>G	p.Thr242Ala	missense_variant	5/5	1	NM_152274.5	P1	Q8N1B3-1

Frequencies

GnomAD3 genomes

AF:

0.00197

AC:

223

AN:

112942

Hom.:

Cov.:

AF XY:

0.00154

AC XY:

AN XY:

35102

show subpopulations

Gnomad AFR

AF:

0.000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000958

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00375

Gnomad OTH

AF:

0.00131

GnomAD3 exomes

AF:

0.00183

AC:

336

AN:

183511

Hom.:

AF XY:

0.00181

AC XY:

123

AN XY:

67939

show subpopulations

Gnomad AFR exome

AF:

0.000532

Gnomad AMR exome

AF:

0.0000365

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000812

Gnomad NFE exome

AF:

0.00381

Gnomad OTH exome

AF:

0.000662

GnomAD4 exome

AF:

0.00285

AC:

3125

AN:

1095790

Hom.:

Cov.:

AF XY:

0.00272

AC XY:

982

AN XY:

361236

show subpopulations

Gnomad4 AFR exome

AF:

0.000379

Gnomad4 AMR exome

AF:

0.0000284

Gnomad4 ASJ exome

AF:

0.000206

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000790

Gnomad4 NFE exome

AF:

0.00358

Gnomad4 OTH exome

AF:

0.00163

GnomAD4 genome

AF:

0.00197

AC:

223

AN:

112996

Hom.:

Cov.:

AF XY:

0.00154

AC XY:

AN XY:

35166

show subpopulations

Gnomad4 AFR

AF:

0.000482

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000958

Gnomad4 NFE

AF:

0.00375

Gnomad4 OTH

AF:

0.00129

Alfa

AF:

0.00209

Hom.:

Bravo

AF:

0.00170

TwinsUK

AF:

0.00512

AC:

ALSPAC

AF:

0.00312

AC:

ESP6500AA

AF:

0.000261

AC:

ESP6500EA

AF:

0.00268

AC:

ExAC

AF:

0.00193

AC:

234

EpiCase

AF:

0.00267

EpiControl

AF:

0.00314

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Nov 19, 2023	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.036

T;.

FATHMM_MKL

Benign

0.62

LIST_S2

Benign

0.49

T;T

M_CAP

Benign

0.015

MetaRNN

Benign

0.010

T;T

MetaSVM

Benign

-0.84

MutationTaster

Benign

0.81

PrimateAI

Benign

0.36

Sift4G

Benign

0.61

T;T

Polyphen

0.0010

B;B

Vest4

0.11

MVP

0.92

ClinPred

0.0089

GERP RS

-1.6

Varity_R

0.056

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

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