9-135821074-C-A

Position:

• chr9-135821074-C-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.3587G>T​(p.Ser1196Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 33)
• Consequence: CAMSAP1 NM_015447.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.37

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=0.14756799).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAMSAP1	NM_015447.4	c.3587G>T	p.Ser1196Ile	missense_variant	11/17	ENST00000389532.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAMSAP1	ENST00000389532.9	c.3587G>T	p.Ser1196Ile	missense_variant	11/17	5	NM_015447.4	P2
CAMSAP1	ENST00000312405.10	c.2753G>T	p.Ser918Ile	missense_variant	9/15	1
CAMSAP1	ENST00000409386.3	c.3620G>T	p.Ser1207Ile	missense_variant	12/18	5		A2
CAMSAP1	ENST00000483991.5	n.2649G>T		non_coding_transcript_exon_variant	4/11	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Jul 27, 2022

Variants in candidate genes are classified as variants of uncertain significance in accordance with ACMG guidelines (Richards et al., 2015); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	17
DANN	Benign	0.85
DEOGEN2	Benign	0.14	T;.;.
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.80	T;T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.15	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L;.;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-2.7	D;D;D
REVEL	Benign	0.046
Sift	Benign	0.095	T;T;T
Sift4G	Benign	0.12	T;T;T
Polyphen		0.80	P;.;P
Vest4		0.15
MutPred		0.31		Loss of phosphorylation at S1196 (P = 0.0222);.;.;
MVP		0.16
MPC		0.20
ClinPred		0.26	T
GERP RS		1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.045
gMVP		0.41

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

LitVar

Other links and lift over

dbSNP: rs749987622; hg19: chr9-138712920;