chr1-229342425-C-T

Position:

• chr1-229342425-C-T

Variant summary

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

The NM_145257.5(CCSAP):​c.41G>A​(p.Arg14His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000391 in 1,278,518 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000039 (0 hom.)
• Consequence: CCSAP NM_145257.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.72

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13697574).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCSAP	NM_145257.5	c.41G>A	p.Arg14His	missense_variant	2/4	ENST00000284617.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCSAP	ENST00000284617.7	c.41G>A	p.Arg14His	missense_variant	2/4	1	NM_145257.5	P1
CCSAP	ENST00000366687.5	c.41G>A	p.Arg14His	missense_variant	1/3	1		P1
CCSAP	ENST00000483092.1	n.472G>A		non_coding_transcript_exon_variant	2/4	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000391 AC: 5 AN: 1278518 Hom.: 0 Cov.: 32 AF XY: 0.00000477 AC XY: 3 AN XY: 629160

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000491

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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

Aug 17, 2021

The c.41G>A (p.R14H) alteration is located in exon 2 (coding exon 1) of the CCSAP gene. This alteration results from a G to A substitution at nucleotide position 41, causing the arginine (R) at amino acid position 14 to be replaced by a histidine (H). 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	Uncertain	0.46
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.062	T;T
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.0091
FATHMM_MKL	Benign	0.57	D
LIST_S2	Benign	0.84	T;.
M_CAP	Uncertain	0.25	D
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	1.7	L;L
MutationTaster	Benign	0.54	N;N;N
PrimateAI	Pathogenic	0.86	D
PROVEAN	Uncertain	-2.4	N;N
REVEL	Benign	0.092
Sift	Uncertain	0.026	D;D
Sift4G	Uncertain	0.010	D;D
Polyphen		0.10	B;B
Vest4		0.18
MutPred		0.18		Loss of MoRF binding (P = 0.0266);Loss of MoRF binding (P = 0.0266);
MVP		0.36
MPC		1.7
ClinPred		0.91	D
GERP RS		3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.21
gMVP		0.18

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: rs201982587; hg19: chr1-229478172;