X-153592235-G-A

Position:

• chrX-153592235-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+271C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0707 in 112,364 control chromosomes in the GnomAD database, including 284 homozygotes. There are 2,223 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., 2223 hem., cov: 24)
• Consequence: CCNQ NM_152274.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.585

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=-0.89).
• BP6: Variant X-153592235-G-A is Benign according to our data. Variant chrX-153592235-G-A is described in ClinVar as [Benign]. Clinvar id is 1221254.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCNQ	NM_152274.5	c.657+271C>T		intron_variant		ENST00000576892.8
CCNQ	NM_001130997.3	c.657+271C>T		intron_variant
CCNQ	XM_011531214.3	c.531+271C>T		intron_variant
CCNQ	XM_047442631.1	c.429+2312C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCNQ	ENST00000576892.8	c.657+271C>T		intron_variant		1	NM_152274.5	P1

Frequencies

GnomAD3 genomes AF: 0.0707 AC: 7944 AN: 112310 Hom.: 284 Cov.: 24 AF XY: 0.0643 AC XY: 2218 AN XY: 34480

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.0117

Gnomad AMR AF: 0.0367

Gnomad ASJ AF: 0.0109

Gnomad EAS AF: 0.0312

Gnomad SAS AF: 0.0493

Gnomad FIN AF: 0.0279

Gnomad MID AF: 0.0377

Gnomad NFE AF: 0.0490

Gnomad OTH AF: 0.0817

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0707 AC: 7949 AN: 112364 Hom.: 284 Cov.: 24 AF XY: 0.0644 AC XY: 2223 AN XY: 34544

Gnomad4 AFR AF: 0.141

Gnomad4 AMR AF: 0.0367

Gnomad4 ASJ AF: 0.0109

Gnomad4 EAS AF: 0.0310

Gnomad4 SAS AF: 0.0483

Gnomad4 FIN AF: 0.0279

Gnomad4 NFE AF: 0.0490

Gnomad4 OTH AF: 0.0807

Alfa AF: 0.0546 Hom.: 1326

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	-0.89
CADD	Benign	0.36
DANN	Benign	0.89

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: rs2280924; hg19: chrX-152857693;