X-153588376-C-T

Position:

• chrX-153588376-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152274.5(CCNQ):​c.736G>A​(p.Glu246Lys) variant causes a missense 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. 9/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 25)
• Consequence: CCNQ NM_152274.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.21

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14522392).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCNQ	NM_152274.5	c.736G>A	p.Glu246Lys	missense_variant	5/5	ENST00000576892.8
CCNQ	NM_001130997.3	c.676G>A	p.Glu226Lys	missense_variant	5/5
CCNQ	XM_011531214.3	c.610G>A	p.Glu204Lys	missense_variant	5/5
CCNQ	XM_047442631.1	c.508G>A	p.Glu170Lys	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCNQ	ENST00000576892.8	c.736G>A	p.Glu246Lys	missense_variant	5/5	1	NM_152274.5	P1

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 25

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 04, 2023

The c.736G>A (p.E246K) alteration is located in exon 5 (coding exon 5) of the FAM58A gene. This alteration results from a G to A substitution at nucleotide position 736, causing the glutamic acid (E) at amino acid position 246 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.023	T;.
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.82	T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-0.94	T
MutationTaster	Benign	0.88	D
PrimateAI	Uncertain	0.64	T
Sift4G	Benign	0.45	T;D
Polyphen		0.027	B;D
Vest4		0.10
MutPred		0.28		Gain of methylation at E246 (P = 0.0068);.;
MVP		0.79
ClinPred		0.80	D
GERP RS		3.5
Varity_R		0.46

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-152853834;