1-229325378-T-C

Variant names:

• chr1-229325378-T-C
• NM_145257.5:c.670A>G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_145257.5(CCSAP):​c.670A>G​(p.Arg224Gly) 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 pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CCSAP NM_145257.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.24

Genes affected

CCSAP (HGNC:29578): (centriole, cilia and spindle associated protein) Enables microtubule binding activity. Involved in mitotic spindle microtubule depolymerization and regulation of mitotic spindle assembly. Located in axon; ciliary transition zone; and cytoskeleton. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.746

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCSAP	NM_145257.5	c.670A>G	p.Arg224Gly	missense_variant	Exon 4 of 4	ENST00000284617.7	NP_660300.3
CCSAP	NM_001410936.1	c.328A>G	p.Arg110Gly	missense_variant	Exon 3 of 3		NP_001397865.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCSAP	ENST00000284617.7	c.670A>G	p.Arg224Gly	missense_variant	Exon 4 of 4	1	NM_145257.5	ENSP00000284617.2
CCSAP	ENST00000366687.5	c.670A>G	p.Arg224Gly	missense_variant	Exon 3 of 3	1		ENSP00000355648.1
CCSAP	ENST00000483092.1	n.1653A>G		non_coding_transcript_exon_variant	Exon 4 of 4	1
CCSAP	ENST00000366686.1	c.328A>G	p.Arg110Gly	missense_variant	Exon 3 of 3	2		ENSP00000355647.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 14, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.670A>G (p.R224G) alteration is located in exon 4 (coding exon 3) of the CCSAP gene. This alteration results from a A to G substitution at nucleotide position 670, causing the arginine (R) at amino acid position 224 to be replaced by a glycine (G). 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	Pathogenic	0.97
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	T;T;.
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.93	D;.;D
M_CAP	Benign	0.040	D
MetaRNN	Pathogenic	0.75	D;D;D
MetaSVM	Benign	-0.41	T
MutationAssessor	Uncertain	2.5	M;M;.
PrimateAI	Benign	0.48	T
PROVEAN	Pathogenic	-5.6	D;D;D
REVEL	Benign	0.28
Sift	Uncertain	0.0050	D;D;D
Sift4G	Uncertain	0.010	D;D;D
Polyphen		0.99	D;D;.
Vest4		0.72
MutPred		0.36		Loss of helix (P = 0.0167);Loss of helix (P = 0.0167);.;
MVP		0.78
MPC		1.4
ClinPred		0.99	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
Varity_R		0.66
gMVP		0.39

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: chr1-229461125;