rs141657773

Variant names:

• chrX-153588388-T-C
• rs141657773
• NM_152274.5:c.724A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_152274.5(CCNQ):​c.724A>G​(p.Thr242Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00277 in 1,208,786 control chromosomes in the GnomAD database, including 7 homozygotes. There are 1,036 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0020 (1 hom., 54 hem., cov: 25)
  • Exomes 𝑓: 0.0029 (6 hom. 982 hem.)
• Consequence: CCNQ NM_152274.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:3
• Conservation: PhyloP100: 1.26
• 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.01023373).
• BP6: Variant X-153588388-T-C is Benign according to our data. Variant chrX-153588388-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 702042.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAd4 at 54 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.724A>G	p.Thr242Ala	missense	Exon 5 of 5	NP_689487.2	Q8N1B3-1
	CCNQ	NM_001130997.3		c.664A>G	p.Thr222Ala	missense	Exon 5 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.724A>G	p.Thr242Ala	missense	Exon 5 of 5	ENSP00000461135.1	Q8N1B3-1
	CCNQ	ENST00000875308.1		c.712A>G	p.Thr238Ala	missense	Exon 5 of 5	ENSP00000545367.1
	CCNQ	ENST00000919978.1		c.694A>G	p.Thr232Ala	missense	Exon 5 of 5	ENSP00000590037.1

Frequencies

GnomAD3 genomes AF: 0.00197 AC: 223 AN: 112942 Hom.: 1 Cov.: 25

Gnomad AFR AF: 0.000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000958

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00375

Gnomad OTH AF: 0.00131

GnomAD2 exomes AF: 0.00183 AC: 336 AN: 183511 AF XY: 0.00181

Gnomad AFR exome AF: 0.000532

Gnomad AMR exome AF: 0.0000365

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000812

Gnomad NFE exome AF: 0.00381

Gnomad OTH exome AF: 0.000662

GnomAD4 exome AF: 0.00285 AC: 3125 AN: 1095790 Hom.: 6 Cov.: 28 AF XY: 0.00272 AC XY: 982 AN XY: 361236

African (AFR) AF: 0.000379 AC: 10 AN: 26356

American (AMR) AF: 0.0000284 AC: 1 AN: 35200

Ashkenazi Jewish (ASJ) AF: 0.000206 AC: 4 AN: 19371

East Asian (EAS) AF: 0.00 AC: 0 AN: 30198

South Asian (SAS) AF: 0.00 AC: 0 AN: 54086

European-Finnish (FIN) AF: 0.000790 AC: 32 AN: 40532

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4121

European-Non Finnish (NFE) AF: 0.00358 AC: 3003 AN: 839911

Other (OTH) AF: 0.00163 AC: 75 AN: 46015

GnomAD4 genome AF: 0.00197 AC: 223 AN: 112996 Hom.: 1 Cov.: 25 AF XY: 0.00154 AC XY: 54 AN XY: 35166

African (AFR) AF: 0.000482 AC: 15 AN: 31140

American (AMR) AF: 0.00 AC: 0 AN: 10781

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2650

East Asian (EAS) AF: 0.00 AC: 0 AN: 3603

South Asian (SAS) AF: 0.00 AC: 0 AN: 2780

European-Finnish (FIN) AF: 0.000958 AC: 6 AN: 6261

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 219

European-Non Finnish (NFE) AF: 0.00375 AC: 200 AN: 53327

Other (OTH) AF: 0.00129 AC: 2 AN: 1550

Alfa AF: 0.00209 Hom.: 19

Bravo AF: 0.00170

TwinsUK AF: 0.00512 AC: 19

ALSPAC AF: 0.00312 AC: 9

ESP6500AA AF: 0.000261 AC: 1

ESP6500EA AF: 0.00268 AC: 18

ExAC AF: 0.00193 AC: 234

EpiCase AF: 0.00267

EpiControl AF: 0.00314

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	15
DANN	Benign	0.95
DEOGEN2	Benign	0.036	T
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.010	T
MetaSVM	Benign	-0.84	T
PhyloP100		1.3
PrimateAI	Benign	0.36	T
Sift4G	Benign	0.61	T
Polyphen		0.0010	B
Vest4		0.11
MVP		0.92
ClinPred		0.0089	T
GERP RS		-1.6
Varity_R		0.056

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: rs141657773; hg19: chrX-152853846;