rs376050298

Positions:

• chrX-153588443-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_152274.5(CCNQ):​c.669C>T​(p.Asp223=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000258 in 1,199,793 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 110 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., 6 hem., cov: 24)
  • Exomes 𝑓: 0.00027 (0 hom. 104 hem.)
• Consequence: CCNQ NM_152274.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.536

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 Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant X-153588443-G-A is Benign according to our data. Variant chrX-153588443-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 445928.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.536 with no splicing effect.
• BS2: High Hemizygotes in GnomAd4 at 6 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCNQ	NM_152274.5	c.669C>T	p.Asp223=	synonymous_variant	5/5	ENST00000576892.8
CCNQ	XM_011531214.3	c.543C>T	p.Asp181=	synonymous_variant	5/5
CCNQ	XM_047442631.1	c.441C>T	p.Asp147=	synonymous_variant	4/4
CCNQ	NM_001130997.3	c.658-49C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCNQ	ENST00000576892.8	c.669C>T	p.Asp223=	synonymous_variant	5/5	1	NM_152274.5	P1

Frequencies

GnomAD3 genomes AF: 0.000115 AC: 13 AN: 112596 Hom.: 0 Cov.: 24 AF XY: 0.000173 AC XY: 6 AN XY: 34734

Gnomad AFR AF: 0.0000968

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000113

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000158 AC: 29 AN: 183102 Hom.: 0 AF XY: 0.000207 AC XY: 14 AN XY: 67616

Gnomad AFR exome AF: 0.000228

Gnomad AMR exome AF: 0.0000365

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000722

Gnomad SAS exome AF: 0.000839

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000858

Gnomad OTH exome AF: 0.000221

GnomAD4 exome AF: 0.000273 AC: 297 AN: 1087144 Hom.: 0 Cov.: 28 AF XY: 0.000295 AC XY: 104 AN XY: 353034

Gnomad4 AFR exome AF: 0.0000764

Gnomad4 AMR exome AF: 0.0000284

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000798

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000297

Gnomad4 OTH exome AF: 0.0000875

GnomAD4 genome AF: 0.000115 AC: 13 AN: 112649 Hom.: 0 Cov.: 24 AF XY: 0.000172 AC XY: 6 AN XY: 34797

Gnomad4 AFR AF: 0.0000966

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00146

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000113

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000356 Hom.: 2

Bravo AF: 0.0000756

EpiCase AF: 0.000382

EpiControl AF: 0.000119

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 13, 2023	- -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Apr 27, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	4.0
DANN	Benign	0.55

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

Other links and lift over

dbSNP: rs376050298; hg19: chrX-152853901;