1-229342254-C-A

Variant names:

• chr1-229342254-C-A
• rs367794347
• NM_145257.5:c.212G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_145257.5(CCSAP):​c.212G>T​(p.Gly71Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000783 in 1,276,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict 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. G71D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000040 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000036 (0 hom.)
• Consequence: CCSAP NM_145257.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.229
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06915918).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145257.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCSAP	NM_145257.5	MANE Select	c.212G>T	p.Gly71Val	missense	Exon 2 of 4	NP_660300.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCSAP	ENST00000284617.7	TSL:1 MANE Select	c.212G>T	p.Gly71Val	missense	Exon 2 of 4	ENSP00000284617.2	Q6IQ19-1
	CCSAP	ENST00000366687.5	TSL:1	c.212G>T	p.Gly71Val	missense	Exon 1 of 3	ENSP00000355648.1	Q6IQ19-1
	CCSAP	ENST00000483092.1	TSL:1	n.643G>T		non_coding_transcript_exon	Exon 2 of 4

Frequencies

GnomAD3 genomes AF: 0.0000396 AC: 6 AN: 151526 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000656

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000355 AC: 4 AN: 1125360 Hom.: 0 Cov.: 32 AF XY: 0.00000370 AC XY: 2 AN XY: 540006

African (AFR) AF: 0.000130 AC: 3 AN: 23148

American (AMR) AF: 0.00 AC: 0 AN: 8826

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15020

East Asian (EAS) AF: 0.00 AC: 0 AN: 26720

South Asian (SAS) AF: 0.00 AC: 0 AN: 32934

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 24012

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3070

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 946396

Other (OTH) AF: 0.0000221 AC: 1 AN: 45234

GnomAD4 genome AF: 0.0000396 AC: 6 AN: 151526 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74016

African (AFR) AF: 0.000121 AC: 5 AN: 41314

American (AMR) AF: 0.0000656 AC: 1 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3456

East Asian (EAS) AF: 0.00 AC: 0 AN: 5104

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10504

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 310

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67790

Other (OTH) AF: 0.00 AC: 0 AN: 2078

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000567

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	9.9
DANN	Benign	0.84
DEOGEN2	Benign	0.021	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.067	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.069	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.6	L
PhyloP100		-0.23
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.047
Sift	Benign	0.097	T
Sift4G	Uncertain	0.037	D
Polyphen		0.078	B
Vest4		0.086
MutPred		0.12		Loss of glycosylation at P72 (P = 0.0952)
MVP		0.067
MPC		1.7
ClinPred		0.15	T
GERP RS		-2.1
PromoterAI		-0.13	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.16
gMVP		0.10
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs367794347; hg19: chr1-229478001;