rs781829925

Variant names:

• chrX-153592581-C-T
• rs781829925
• NM_152274.5:c.582G>A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_152274.5(CCNQ):​c.582G>A​(p.Ala194Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000909 in 1,210,729 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.000044 (0 hom., 2 hem., cov: 24)
  • Exomes 𝑓: 0.0000055 (0 hom. 2 hem.)
• Consequence: CCNQ NM_152274.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.27
• Publications: 0 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.14).
• BP6: Variant X-153592581-C-T is Benign according to our data. Variant chrX-153592581-C-T is described in ClinVar as Benign. ClinVar VariationId is 1574003.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.27 with no splicing effect.
• BS2: High Hemizygotes in GnomAd4 at 2 XL gene

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.582G>A	p.Ala194Ala	synonymous	Exon 4 of 5	NP_689487.2	Q8N1B3-1
	CCNQ	NM_001130997.3		c.582G>A	p.Ala194Ala	synonymous	Exon 4 of 5	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.582G>A	p.Ala194Ala	synonymous	Exon 4 of 5	ENSP00000461135.1	Q8N1B3-1
	CCNQ	ENST00000875308.1		c.570G>A	p.Ala190Ala	synonymous	Exon 4 of 5	ENSP00000545367.1
	CCNQ	ENST00000919978.1		c.552G>A	p.Ala184Ala	synonymous	Exon 4 of 5	ENSP00000590037.1

Frequencies

GnomAD3 genomes AF: 0.0000442 AC: 5 AN: 113115 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.0000321

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000185

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000375

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000111 AC: 2 AN: 180283 AF XY: 0.0000304

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000547 AC: 6 AN: 1097614 Hom.: 0 Cov.: 31 AF XY: 0.00000551 AC XY: 2 AN XY: 363126

African (AFR) AF: 0.00 AC: 0 AN: 26397

American (AMR) AF: 0.00 AC: 0 AN: 35185

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19355

East Asian (EAS) AF: 0.00 AC: 0 AN: 30188

South Asian (SAS) AF: 0.0000370 AC: 2 AN: 54067

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40347

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4107

European-Non Finnish (NFE) AF: 0.00000356 AC: 3 AN: 841913

Other (OTH) AF: 0.0000217 AC: 1 AN: 46055

GnomAD4 genome AF: 0.0000442 AC: 5 AN: 113115 Hom.: 0 Cov.: 24 AF XY: 0.0000567 AC XY: 2 AN XY: 35263

African (AFR) AF: 0.0000321 AC: 1 AN: 31188

American (AMR) AF: 0.000185 AC: 2 AN: 10829

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2656

East Asian (EAS) AF: 0.00 AC: 0 AN: 3578

South Asian (SAS) AF: 0.00 AC: 0 AN: 2793

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6296

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 237

European-Non Finnish (NFE) AF: 0.0000375 AC: 2 AN: 53321

Other (OTH) AF: 0.00 AC: 0 AN: 1529

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000302

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	-0.57
CADD	Benign	0.096
DANN	Benign	0.87
PhyloP100		-2.3

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: rs781829925; hg19: chrX-152858039; COSMIC: COSV99367943; COSMIC: COSV99367943;