NM_152274.5:c.724A>G

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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. 11/15 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

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 -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 id is 702042.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-153588388-T-C is described in Lovd as [Likely_benign].
• BS2: High Hemizygotes in GnomAd4 at 54 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCNQ	NM_152274.5	c.724A>G	p.Thr242Ala	missense_variant	Exon 5 of 5	ENST00000576892.8	NP_689487.2
CCNQ	NM_001130997.3	c.664A>G	p.Thr222Ala	missense_variant	Exon 5 of 5		NP_001124469.1
CCNQ	XM_011531214.3	c.598A>G	p.Thr200Ala	missense_variant	Exon 5 of 5		XP_011529516.1
CCNQ	XM_047442631.1	c.496A>G	p.Thr166Ala	missense_variant	Exon 4 of 4		XP_047298587.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCNQ	ENST00000576892.8	c.724A>G	p.Thr242Ala	missense_variant	Exon 5 of 5	1	NM_152274.5	ENSP00000461135.1

Frequencies

GnomAD3 genomes AF: 0.00197 AC: 223 AN: 112942 Hom.: 1 Cov.: 25 AF XY: 0.00154 AC XY: 54 AN XY: 35102

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

GnomAD3 exomes AF: 0.00183 AC: 336 AN: 183511 Hom.: 0 AF XY: 0.00181 AC XY: 123 AN XY: 67939

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 SAS 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

Gnomad4 AFR exome AF: 0.000379

Gnomad4 AMR exome AF: 0.0000284

Gnomad4 ASJ exome AF: 0.000206

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000790

Gnomad4 NFE exome AF: 0.00358

Gnomad4 OTH exome AF: 0.00163

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

Gnomad4 AFR AF: 0.000482

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000958

Gnomad4 NFE AF: 0.00375

Gnomad4 OTH AF: 0.00129

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

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:3

-

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Dec 04, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

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;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.010	T;T
MetaSVM	Benign	-0.84	T
PrimateAI	Benign	0.36	T
Sift4G	Benign	0.61	T;T
Polyphen		0.0010	B;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

Publications

LitVar

Other links and lift over

dbSNP: rs141657773; hg19: chrX-152853846;