X-153588370-G-A

Position:

• chrX-153588370-G-A

Variant summary

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

The ENST00000576892.8(CCNQ):​c.742C>T​(p.Pro248Ser) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 25)
• Consequence: CCNQ ENST00000576892.8 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.27

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=0.21794245).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCNQ	NM_152274.5	c.742C>T	p.Pro248Ser	missense_variant	5/5	ENST00000576892.8	NP_689487.2
CCNQ	NM_001130997.3	c.682C>T	p.Pro228Ser	missense_variant	5/5		NP_001124469.1
CCNQ	XM_011531214.3	c.616C>T	p.Pro206Ser	missense_variant	5/5		XP_011529516.1
CCNQ	XM_047442631.1	c.514C>T	p.Pro172Ser	missense_variant	4/4		XP_047298587.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCNQ	ENST00000576892.8	c.742C>T	p.Pro248Ser	missense_variant	5/5	1	NM_152274.5	ENSP00000461135	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

Jul 26, 2022

The c.742C>T (p.P248S) alteration is located in exon 5 (coding exon 5) of the FAM58A gene. This alteration results from a C to T substitution at nucleotide position 742, causing the proline (P) at amino acid position 248 to be replaced by a serine (S). 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	0.21
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.016	T;.
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.82	T;T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.22	T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.92	N
PrimateAI	Uncertain	0.52	T
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;D
Vest4		0.13
MutPred		0.30		Gain of glycosylation at P248 (P = 0.0129);.;
MVP		0.91
ClinPred		0.92	D
GERP RS		3.6
Varity_R		0.10

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-152853828;