1-229326791-C-G

Variant names:

• chr1-229326791-C-G
• rs747189562
• NM_145257.5:c.583G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_145257.5(CCSAP):​c.583G>C​(p.Asp195His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D195N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: CCSAP NM_145257.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.05

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30222973).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCSAP	NM_145257.5	c.583G>C	p.Asp195His	missense_variant	Exon 3 of 4	ENST00000284617.7	NP_660300.3
CCSAP	NM_001410936.1	c.241G>C	p.Asp81His	missense_variant	Exon 2 of 3		NP_001397865.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCSAP	ENST00000284617.7	c.583G>C	p.Asp195His	missense_variant	Exon 3 of 4	1	NM_145257.5	ENSP00000284617.2
CCSAP	ENST00000366687.5	c.583G>C	p.Asp195His	missense_variant	Exon 2 of 3	1		ENSP00000355648.1
CCSAP	ENST00000483092.1	n.1566G>C		non_coding_transcript_exon_variant	Exon 3 of 4	1
CCSAP	ENST00000366686.1	c.241G>C	p.Asp81His	missense_variant	Exon 2 of 3	2		ENSP00000355647.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000278 AC: 7 AN: 251378 Hom.: 0 AF XY: 0.0000368 AC XY: 5 AN XY: 135878

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000381

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461890 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727248

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000126

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000113

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.49
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	T;T;.
Eigen	Benign	0.11
Eigen_PC	Benign	-0.028
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Uncertain	0.86	D;.;D
M_CAP	Benign	0.068	D
MetaRNN	Benign	0.30	T;T;T
MetaSVM	Benign	-0.47	T
MutationAssessor	Uncertain	2.5	M;M;.
PrimateAI	Uncertain	0.56	T
PROVEAN	Pathogenic	-4.8	D;D;D
REVEL	Uncertain	0.30
Sift	Uncertain	0.0090	D;D;D
Sift4G	Uncertain	0.014	D;D;D
Polyphen		1.0	D;D;.
Vest4		0.42
MutPred		0.40		Gain of MoRF binding (P = 0.0728);Gain of MoRF binding (P = 0.0728);.;
MVP		0.60
MPC		1.4
ClinPred		0.90	D
GERP RS		4.5
Varity_R		0.49
gMVP		0.19

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: rs747189562; hg19: chr1-229462538;