X-153592536-G-T

Variant names:

• chrX-153592536-G-T
• rs139186601
• NM_152274.5:c.627C>A

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_152274.5(CCNQ):​c.627C>A​(p.Ala209Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 25)
• Consequence: CCNQ NM_152274.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.442

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 Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP7: Synonymous conserved (PhyloP=-0.442 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCNQ	NM_152274.5	c.627C>A	p.Ala209Ala	synonymous_variant	Exon 4 of 5	ENST00000576892.8	NP_689487.2
CCNQ	NM_001130997.3	c.627C>A	p.Ala209Ala	synonymous_variant	Exon 4 of 5		NP_001124469.1
CCNQ	XM_011531214.3	c.501C>A	p.Ala167Ala	synonymous_variant	Exon 4 of 5		XP_011529516.1
CCNQ	XM_047442631.1	c.429+2011C>A		intron_variant	Intron 3 of 3		XP_047298587.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCNQ	ENST00000576892.8	c.627C>A	p.Ala209Ala	synonymous_variant	Exon 4 of 5	1	NM_152274.5	ENSP00000461135.1

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 25

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.28
DANN	Benign	0.48

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: rs139186601; hg19: chrX-152857994;