NM_020902.2:c.269A>C

Variant names:

• chr19-7605346-A-C
• NM_020902.2:c.269A>C

Variant summary

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

The NM_020902.2(CAMSAP3):​c.269A>C​(p.Gln90Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: 30)
• Consequence: CAMSAP3 NM_020902.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.59

Genes affected

CAMSAP3 (HGNC:29307): (calmodulin regulated spectrin associated protein family member 3) Enables actin filament binding activity and microtubule minus-end binding activity. Involved in several processes, including microtubule cytoskeleton organization; regulation of organelle organization; and zonula adherens maintenance. Located in cytoplasm; nucleoplasm; and zonula adherens. Colocalizes with centrosome and microtubule minus-end. [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, 0.75

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAMSAP3	NM_020902.2	c.269A>C	p.Gln90Pro	missense_variant	Exon 2 of 17	ENST00000160298.9	NP_065953.1
CAMSAP3	NM_001080429.3	c.269A>C	p.Gln90Pro	missense_variant	Exon 2 of 19		NP_001073898.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAMSAP3	ENST00000160298.9	c.269A>C	p.Gln90Pro	missense_variant	Exon 2 of 17	2	NM_020902.2	ENSP00000160298.3
CAMSAP3	ENST00000446248.4	c.269A>C	p.Gln90Pro	missense_variant	Exon 2 of 19	1		ENSP00000416797.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 13, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.269A>C (p.Q90P) alteration is located in exon 2 (coding exon 2) of the CAMSAP3 gene. This alteration results from a A to C substitution at nucleotide position 269, causing the glutamine (Q) at amino acid position 90 to be replaced by a proline (P). 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	0.55
BayesDel_addAF	Uncertain	0.017	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.060	T;.
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.78	T;T
M_CAP	Benign	0.015	T
MetaRNN	Pathogenic	0.75	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L;L
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-1.7	N;N
REVEL	Benign	0.20
Sift	Uncertain	0.027	D;D
Sift4G	Benign	0.088	T;T
Polyphen		0.99	D;D
Vest4		0.74
MutPred		0.52		Loss of helix (P = 0.0444);Loss of helix (P = 0.0444);
MVP		0.63
MPC		1.7
ClinPred		0.53	D
GERP RS		3.3
Varity_R		0.34
gMVP		0.82

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: chr19-7670232;