19-7606314-C-T

Variant names:

• chr19-7606314-C-T
• rs1568441817
• NM_020902.2:c.446C>T

Variant summary

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

The NM_020902.2(CAMSAP3):​c.446C>T​(p.Ala149Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,194 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
• Consequence: CAMSAP3 NM_020902.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.67

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23830318).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAMSAP3	NM_020902.2	c.446C>T	p.Ala149Val	missense_variant	Exon 3 of 17	ENST00000160298.9	NP_065953.1
CAMSAP3	NM_001080429.3	c.446C>T	p.Ala149Val	missense_variant	Exon 3 of 19		NP_001073898.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAMSAP3	ENST00000160298.9	c.446C>T	p.Ala149Val	missense_variant	Exon 3 of 17	2	NM_020902.2	ENSP00000160298.3
CAMSAP3	ENST00000446248.4	c.446C>T	p.Ala149Val	missense_variant	Exon 3 of 19	1		ENSP00000416797.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152194 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 35

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152194 Hom.: 0 Cov.: 31 AF XY: 0.0000134 AC XY: 1 AN XY: 74352

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 03, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.446C>T (p.A149V) alteration is located in exon 3 (coding exon 3) of the CAMSAP3 gene. This alteration results from a C to T substitution at nucleotide position 446, causing the alanine (A) at amino acid position 149 to be replaced by a valine (V). 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	0.17
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.038	T;.
Eigen	Benign	0.19
Eigen_PC	Benign	0.22
FATHMM_MKL	Benign	0.76	D
LIST_S2	Uncertain	0.86	D;D
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.24	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L;L
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.9	N;N
REVEL	Benign	0.10
Sift	Uncertain	0.0040	D;D
Sift4G	Uncertain	0.016	D;D
Polyphen		0.96	D;B
Vest4		0.46
MutPred		0.40		Loss of ubiquitination at K154 (P = 0.1322);Loss of ubiquitination at K154 (P = 0.1322);
MVP		0.32
MPC		1.3
ClinPred		0.90	D
GERP RS		4.1
Varity_R		0.21
gMVP		0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1568441817; hg19: chr19-7671200;