Variant chrX-153592661-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The ENST00000576892.8(CCNQ):c.502G>T(p.Val168Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000661 in 1,210,384 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 6 hemizygotes 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 Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V168I) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000035 ( 0 hom., 3 hem., cov: 24)

Exomes 𝑓: 0.0000036 ( 0 hom. 3 hem. )

Consequence

CCNQ
ENST00000576892.8 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.964

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07065034).

BP6

Variant X-153592661-C-A is Benign according to our data. Variant chrX-153592661-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 1947874.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 3 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CCNQ	NM_152274.5 linkuse as main transcript	c.502G>T	p.Val168Phe	missense_variant	4/5	ENST00000576892.8	NP_689487.2
CCNQ	NM_001130997.3 linkuse as main transcript	c.502G>T	p.Val168Phe	missense_variant	4/5		NP_001124469.1
CCNQ	XM_011531214.3 linkuse as main transcript	c.376G>T	p.Val126Phe	missense_variant	4/5		XP_011529516.1
CCNQ	XM_047442631.1 linkuse as main transcript	c.429+1886G>T		intron_variant			XP_047298587.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCNQ	ENST00000576892.8 linkuse as main transcript	c.502G>T	p.Val168Phe	missense_variant	4/5	1	NM_152274.5	ENSP00000461135	P1	Q8N1B3-1

Frequencies

GnomAD3 genomes

AF:

0.0000353

AC:

AN:

113266

Hom.:

Cov.:

AF XY:

0.0000847

AC XY:

AN XY:

35410

show subpopulations

Gnomad AFR

AF:

0.0000961

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000358

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000225

AC:

AN:

177487

Hom.:

AF XY:

0.0000314

AC XY:

AN XY:

63631

show subpopulations

Gnomad AFR exome

AF:

0.000157

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000108

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000365

AC:

AN:

1097065

Hom.:

Cov.:

AF XY:

0.00000828

AC XY:

AN XY:

362527

show subpopulations

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:

0.0000557

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000217

GnomAD4 genome

AF:

0.0000353

AC:

AN:

113319

Hom.:

Cov.:

AF XY:

0.0000846

AC XY:

AN XY:

35473

show subpopulations

Gnomad4 AFR

AF:

0.0000958

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000359

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Oct 08, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.033

T;.;.

FATHMM_MKL

Benign

0.44

LIST_S2

Uncertain

0.88

D;D;D

M_CAP

Benign

0.022

MetaRNN

Benign

0.071

T;T;T

MetaSVM

Benign

-0.97

MutationTaster

Benign

0.65

PrimateAI

Uncertain

0.51

Sift4G

Uncertain

0.053

T;T;.

Polyphen

0.92

P;P;.

Vest4

0.44

MutPred

0.44

Loss of MoRF binding (P = 0.0862);Loss of MoRF binding (P = 0.0862);.;

MVP

0.45

ClinPred

0.18

GERP RS

2.6

Varity_R

0.098

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