1-229342270-A-C

Position:

• chr1-229342270-A-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_145257.5(CCSAP):​c.196T>G​(p.Ser66Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000011 in 1,179,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: CCSAP NM_145257.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0120

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.035976708).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCSAP	NM_145257.5	c.196T>G	p.Ser66Ala	missense_variant	2/4	ENST00000284617.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCSAP	ENST00000284617.7	c.196T>G	p.Ser66Ala	missense_variant	2/4	1	NM_145257.5	P1
CCSAP	ENST00000366687.5	c.196T>G	p.Ser66Ala	missense_variant	1/3	1		P1
CCSAP	ENST00000483092.1	n.627T>G		non_coding_transcript_exon_variant	2/4	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000110 AC: 13 AN: 1179876 Hom.: 0 Cov.: 32 AF XY: 0.0000105 AC XY: 6 AN XY: 573132

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: 0.0000133

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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 13, 2021

The c.196T>G (p.S66A) alteration is located in exon 2 (coding exon 1) of the CCSAP gene. This alteration results from a T to G substitution at nucleotide position 196, causing the serine (S) at amino acid position 66 to be replaced by an alanine (A). 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	0.084
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	8.5
DANN	Benign	0.47
DEOGEN2	Benign	0.021	T;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.22	T;.
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.036	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L;L
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-0.94	N;N
REVEL	Benign	0.075
Sift	Benign	1.0	T;T
Sift4G	Benign	0.73	T;T
Polyphen		0.0	B;B
Vest4		0.049
MutPred		0.071		Loss of phosphorylation at S66 (P = 0.0043);Loss of phosphorylation at S66 (P = 0.0043);
MVP		0.11
MPC		1.2
ClinPred		0.080	T
GERP RS		0.073
Varity_R		0.064
gMVP		0.13

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: chr1-229478017;