rs12010175

Variant names:

• chrX-153597180-A-G
• rs12010175
• NM_152274.5:c.113-993T>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_152274.5(CCNQ):​c.113-993T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.89 (31001 hom., 28928 hem., cov: 23)
  • Failed GnomAD Quality Control
• Consequence: CCNQ NM_152274.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.28
• Publications: 25 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, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCNQ	NM_152274.5	c.113-993T>C		intron_variant	Intron 1 of 4	ENST00000576892.8	NP_689487.2
CCNQ	NM_001130997.3	c.113-993T>C		intron_variant	Intron 1 of 4		NP_001124469.1
CCNQ	XM_011531214.3	c.-15+242T>C		intron_variant	Intron 1 of 4		XP_011529516.1
CCNQ	XM_047442631.1	c.113-993T>C		intron_variant	Intron 1 of 3		XP_047298587.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCNQ	ENST00000576892.8	c.113-993T>C		intron_variant	Intron 1 of 4	1	NM_152274.5	ENSP00000461135.1

Frequencies

GnomAD3 genomes AF: 0.889 AC: 98152 AN: 110376 Hom.: 31005 Cov.: 23

Gnomad AFR AF: 0.809

Gnomad AMI AF: 0.926

Gnomad AMR AF: 0.829

Gnomad ASJ AF: 0.962

Gnomad EAS AF: 0.835

Gnomad SAS AF: 0.824

Gnomad FIN AF: 0.922

Gnomad MID AF: 0.958

Gnomad NFE AF: 0.945

Gnomad OTH AF: 0.910

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.889 AC: 98187 AN: 110428 Hom.: 31001 Cov.: 23 AF XY: 0.886 AC XY: 28928 AN XY: 32634

African (AFR) AF: 0.809 AC: 24434 AN: 30219

American (AMR) AF: 0.829 AC: 8627 AN: 10411

Ashkenazi Jewish (ASJ) AF: 0.962 AC: 2540 AN: 2640

East Asian (EAS) AF: 0.835 AC: 2935 AN: 3517

South Asian (SAS) AF: 0.825 AC: 2134 AN: 2586

European-Finnish (FIN) AF: 0.922 AC: 5320 AN: 5770

Middle Eastern (MID) AF: 0.954 AC: 206 AN: 216

European-Non Finnish (NFE) AF: 0.945 AC: 49993 AN: 52886

Other (OTH) AF: 0.911 AC: 1376 AN: 1511

Alfa AF: 0.910 Hom.: 95526

Bravo AF: 0.879

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	9.7
DANN	Benign	0.62
PhyloP100		1.3

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: rs12010175; hg19: chrX-152862638;