rs747189562

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr1-229326791-C-A
• chr1-229326791-C-G
• chr1-229326791-C-T

Variant summary

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

The NM_145257.5(CCSAP):​c.583G>T​(p.Asp195Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 32)
  • Exomes 𝑓: 0.0000014 (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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.751

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCSAP	NM_145257.5	c.583G>T	p.Asp195Tyr	missense_variant	Exon 3 of 4	ENST00000284617.7	NP_660300.3
CCSAP	NM_001410936.1	c.241G>T	p.Asp81Tyr	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>T	p.Asp195Tyr	missense_variant	Exon 3 of 4	1	NM_145257.5	ENSP00000284617.2
CCSAP	ENST00000366687.5	c.583G>T	p.Asp195Tyr	missense_variant	Exon 2 of 3	1		ENSP00000355648.1
CCSAP	ENST00000483092.1	n.1566G>T		non_coding_transcript_exon_variant	Exon 3 of 4	1
CCSAP	ENST00000366686.1	c.241G>T	p.Asp81Tyr	missense_variant	Exon 2 of 3	2		ENSP00000355647.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461890 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 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: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.10	T;T;.
Eigen	Benign	0.11
Eigen_PC	Benign	-0.028
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Uncertain	0.86	D;.;D
M_CAP	Uncertain	0.097	D
MetaRNN	Pathogenic	0.75	D;D;D
MetaSVM	Benign	-0.47	T
MutationAssessor	Uncertain	2.5	M;M;.
PrimateAI	Uncertain	0.54	T
PROVEAN	Pathogenic	-6.3	D;D;D
REVEL	Uncertain	0.36
Sift	Uncertain	0.0060	D;D;D
Sift4G	Uncertain	0.0090	D;D;D
Polyphen		1.0	D;D;.
Vest4		0.61
MVP		0.55
MPC		1.4
ClinPred		0.98	D
GERP RS		4.5
Varity_R		0.60
gMVP		0.27

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: chr1-229462538;