X-153592590-G-A

Variant names:

• chrX-153592590-G-A
• rs200558104
• NM_152274.5:c.573C>T

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.573C>T​(p.Ile191Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0003 in 1,210,804 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 103 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00022 (0 hom., 6 hem., cov: 25)
  • Exomes 𝑓: 0.00031 (0 hom. 97 hem.)
• Consequence: CCNQ NM_152274.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.00300
• 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: Orphanet, G2P, Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.033).
• BP6: Variant X-153592590-G-A is Benign according to our data. Variant chrX-153592590-G-A is described in ClinVar as Benign. ClinVar VariationId is 698184.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.003 with no splicing effect.
• BS2: High Hemizygotes in GnomAd4 at 6 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.573C>T	p.Ile191Ile	synonymous	Exon 4 of 5	NP_689487.2	Q8N1B3-1
	CCNQ	NM_001130997.3		c.573C>T	p.Ile191Ile	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.573C>T	p.Ile191Ile	synonymous	Exon 4 of 5	ENSP00000461135.1	Q8N1B3-1
	CCNQ	ENST00000875308.1		c.561C>T	p.Ile187Ile	synonymous	Exon 4 of 5	ENSP00000545367.1
	CCNQ	ENST00000919978.1		c.543C>T	p.Ile181Ile	synonymous	Exon 4 of 5	ENSP00000590037.1

Frequencies

GnomAD3 genomes AF: 0.000221 AC: 25 AN: 113242 Hom.: 0 Cov.: 25

Gnomad AFR AF: 0.000128

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000553

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: 0.000281

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000289 AC: 52 AN: 180123 AF XY: 0.000274

Gnomad AFR exome AF: 0.0000776

Gnomad AMR exome AF: 0.000734

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000729

Gnomad FIN exome AF: 0.0000636

Gnomad NFE exome AF: 0.000363

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000308 AC: 338 AN: 1097562 Hom.: 0 Cov.: 31 AF XY: 0.000267 AC XY: 97 AN XY: 363090

African (AFR) AF: 0.000114 AC: 3 AN: 26396

American (AMR) AF: 0.000768 AC: 27 AN: 35167

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19350

East Asian (EAS) AF: 0.0000331 AC: 1 AN: 30186

South Asian (SAS) AF: 0.00 AC: 0 AN: 54039

European-Finnish (FIN) AF: 0.0000495 AC: 2 AN: 40385

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4106

European-Non Finnish (NFE) AF: 0.000342 AC: 288 AN: 841863

Other (OTH) AF: 0.000369 AC: 17 AN: 46070

GnomAD4 genome AF: 0.000221 AC: 25 AN: 113242 Hom.: 0 Cov.: 25 AF XY: 0.000170 AC XY: 6 AN XY: 35362

African (AFR) AF: 0.000128 AC: 4 AN: 31237

American (AMR) AF: 0.000553 AC: 6 AN: 10845

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2661

East Asian (EAS) AF: 0.00 AC: 0 AN: 3591

South Asian (SAS) AF: 0.00 AC: 0 AN: 2788

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6325

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 239

European-Non Finnish (NFE) AF: 0.000281 AC: 15 AN: 53335

Other (OTH) AF: 0.00 AC: 0 AN: 1536

Alfa AF: 0.000217 Hom.: 0

Bravo AF: 0.000423

ClinVar

ClinVar submissions

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	-0.53
CADD	Benign	2.3
DANN	Benign	0.83
PhyloP100		-0.0030

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: rs200558104; hg19: chrX-152858048; COSMIC: COSV52344718; COSMIC: COSV52344718;