9-135818506-C-T

Variant names:

• chr9-135818506-C-T
• NM_015447.4:c.4070G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015447.4(CAMSAP1):​c.4070G>A​(p.Gly1357Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,102 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign 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: 6.9e-7 (0 hom.)
• Consequence: CAMSAP1 NM_015447.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.84

Genes affected

CAMSAP1 (HGNC:19946): (calmodulin regulated spectrin associated protein 1) Enables microtubule minus-end binding activity and spectrin binding activity. Involved in several processes, including neuron projection development; regulation of cell morphogenesis; and regulation of microtubule polymerization. Located in microtubule. Colocalizes with microtubule minus-end. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22804087).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAMSAP1	NM_015447.4	c.4070G>A	p.Gly1357Glu	missense_variant	Exon 13 of 17	ENST00000389532.9	NP_056262.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAMSAP1	ENST00000389532.9	c.4070G>A	p.Gly1357Glu	missense_variant	Exon 13 of 17	5	NM_015447.4	ENSP00000374183.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459102 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 725990

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: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Dec 11, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.4070G>A (p.G1357E) alteration is located in exon 13 (coding exon 13) of the CAMSAP1 gene. This alteration results from a G to A substitution at nucleotide position 4070, causing the glycine (G) at amino acid position 1357 to be replaced by a glutamic acid (E). 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	0.25
BayesDel_addAF	Benign	-0.090	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.058	T;.;.
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.95	D;D;D
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.23	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L;.;.
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-1.1	N;N;N
REVEL	Benign	0.17
Sift	Uncertain	0.029	D;T;T
Sift4G	Benign	0.50	T;T;T
Polyphen		1.0	D;.;P
Vest4		0.38
MutPred		0.36		Gain of helix (P = 0.0093);.;.;
MVP		0.22
MPC		1.2
ClinPred		0.83	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.14
gMVP		0.54

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: chr9-138710352;