chrX-153592235-G-A

Variant names:

• chrX-153592235-G-A
• rs2280924
• NM_152274.5:c.657+271C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• syndactyly-telecanthus-anogenital and renal malformations syndrome

  Inheritance: XL Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), G2P, Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152274.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCNQ	NM_152274.5	MANE Select	c.657+271C>T		intron	N/A	NP_689487.2	Q8N1B3-1
	CCNQ	NM_001130997.3		c.657+271C>T		intron	N/A	NP_001124469.1	Q8N1B3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCNQ	ENST00000576892.8	TSL:1 MANE Select	c.657+271C>T		intron	N/A	ENSP00000461135.1	Q8N1B3-1
	CCNQ	ENST00000875308.1		c.645+271C>T		intron	N/A	ENSP00000545367.1
	CCNQ	ENST00000919978.1		c.627+271C>T		intron	N/A	ENSP00000590037.1

Frequencies

GnomAD3 genomes AF: 0.0707 AC: 7944 AN: 112310 Hom.: 284 Cov.: 24

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

African (AFR) AF: 0.141 AC: 4365 AN: 30894

American (AMR) AF: 0.0367 AC: 394 AN: 10747

Ashkenazi Jewish (ASJ) AF: 0.0109 AC: 29 AN: 2657

East Asian (EAS) AF: 0.0310 AC: 110 AN: 3549

South Asian (SAS) AF: 0.0483 AC: 132 AN: 2733

European-Finnish (FIN) AF: 0.0279 AC: 172 AN: 6158

Middle Eastern (MID) AF: 0.0321 AC: 7 AN: 218

European-Non Finnish (NFE) AF: 0.0490 AC: 2608 AN: 53185

Other (OTH) AF: 0.0807 AC: 124 AN: 1537

Alfa AF: 0.0589 Hom.: 2126

Bravo AF: 0.0750

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.36
DANN	Benign	0.89
PhyloP100		-0.58

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

Other links and lift over

dbSNP: rs2280924; hg19: chrX-152857693;