chrX-153592362-G-A

Position:

• chrX-153592362-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_152274.5(CCNQ):​c.657+144C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0551 in 601,518 control chromosomes in the GnomAD database, including 856 homozygotes. There are 9,714 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.071 (284 hom., 2330 hem., cov: 25)
  • Exomes 𝑓: 0.051 (572 hom. 7384 hem.)
• Consequence: CCNQ NM_152274.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.23

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant X-153592362-G-A is Benign according to our data. Variant chrX-153592362-G-A is described in ClinVar as [Benign]. Clinvar id is 1275895.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCNQ	NM_152274.5	c.657+144C>T		intron_variant		ENST00000576892.8
CCNQ	NM_001130997.3	c.657+144C>T		intron_variant
CCNQ	XM_011531214.3	c.531+144C>T		intron_variant
CCNQ	XM_047442631.1	c.429+2185C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCNQ	ENST00000576892.8	c.657+144C>T		intron_variant		1	NM_152274.5	P1

Frequencies

GnomAD3 genomes AF: 0.0712 AC: 8056 AN: 113111 Hom.: 284 Cov.: 25 AF XY: 0.0660 AC XY: 2325 AN XY: 35247

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.0117

Gnomad AMR AF: 0.0370

Gnomad ASJ AF: 0.0113

Gnomad EAS AF: 0.0299

Gnomad SAS AF: 0.0495

Gnomad FIN AF: 0.0302

Gnomad MID AF: 0.0336

Gnomad NFE AF: 0.0493

Gnomad OTH AF: 0.0804

GnomAD4 exome AF: 0.0513 AC: 25070 AN: 488353 Hom.: 572 AF XY: 0.0527 AC XY: 7384 AN XY: 140105

Gnomad4 AFR exome AF: 0.153

Gnomad4 AMR exome AF: 0.0288

Gnomad4 ASJ exome AF: 0.00948

Gnomad4 EAS exome AF: 0.0329

Gnomad4 SAS exome AF: 0.0541

Gnomad4 FIN exome AF: 0.0288

Gnomad4 NFE exome AF: 0.0529

Gnomad4 OTH exome AF: 0.0517

GnomAD4 genome AF: 0.0712 AC: 8061 AN: 113165 Hom.: 284 Cov.: 25 AF XY: 0.0660 AC XY: 2330 AN XY: 35311

Gnomad4 AFR AF: 0.142

Gnomad4 AMR AF: 0.0369

Gnomad4 ASJ AF: 0.0113

Gnomad4 EAS AF: 0.0297

Gnomad4 SAS AF: 0.0485

Gnomad4 FIN AF: 0.0302

Gnomad4 NFE AF: 0.0493

Gnomad4 OTH AF: 0.0794

Alfa AF: 0.0485 Hom.: 2683

Bravo AF: 0.0750

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.082
DANN	Benign	0.70

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: rs2280925; hg19: chrX-152857820;