chr19-7606303-G-A

Position:

• chr19-7606303-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_020902.2(CAMSAP3):​c.435G>A​(p.Met145Ile) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: CAMSAP3 NM_020902.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.05

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.868

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAMSAP3	NM_020902.2	c.435G>A	p.Met145Ile	missense_variant	3/17	ENST00000160298.9	NP_065953.1
CAMSAP3	NM_001080429.3	c.435G>A	p.Met145Ile	missense_variant	3/19		NP_001073898.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAMSAP3	ENST00000160298.9	c.435G>A	p.Met145Ile	missense_variant	3/17	2	NM_020902.2	ENSP00000160298.3
CAMSAP3	ENST00000446248.4	c.435G>A	p.Met145Ile	missense_variant	3/19	1		ENSP00000416797.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 31

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

Apr 14, 2022

The c.435G>A (p.M145I) alteration is located in exon 3 (coding exon 3) of the CAMSAP3 gene. This alteration results from a G to A substitution at nucleotide position 435, causing the methionine (M) at amino acid position 145 to be replaced by an isoleucine (I). 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	Pathogenic	0.98
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.54	D;.
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.90	D;D
M_CAP	Benign	0.072	D
MetaRNN	Pathogenic	0.87	D;D
MetaSVM	Benign	-0.57	T
MutationAssessor	Uncertain	2.8	M;M
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-3.6	D;D
REVEL	Uncertain	0.40
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.0020	D;D
Polyphen		0.99	D;P
Vest4		0.84
MutPred		0.65		Loss of catalytic residue at M145 (P = 0.2764);Loss of catalytic residue at M145 (P = 0.2764);
MVP		0.59
MPC		1.8
ClinPred		0.99	D
GERP RS		4.1
Varity_R		0.78
gMVP		0.88

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.40		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.40		Position offset: 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: chr19-7671189;