NM_020902.2:c.166C>A

Variant names:

• chr19-7605243-C-A
• NM_020902.2:c.166C>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_020902.2(CAMSAP3):​c.166C>A​(p.Leu56Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000071 in 1,408,224 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: CAMSAP3 NM_020902.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.04
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020902.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAMSAP3	NM_020902.2	MANE Select	c.166C>A	p.Leu56Met	missense	Exon 2 of 17	NP_065953.1	Q9P1Y5-1
	CAMSAP3	NM_001080429.3		c.166C>A	p.Leu56Met	missense	Exon 2 of 19	NP_001073898.1	Q9P1Y5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAMSAP3	ENST00000160298.9	TSL:2 MANE Select	c.166C>A	p.Leu56Met	missense	Exon 2 of 17	ENSP00000160298.3	Q9P1Y5-1
	CAMSAP3	ENST00000446248.4	TSL:1	c.166C>A	p.Leu56Met	missense	Exon 2 of 19	ENSP00000416797.1	Q9P1Y5-2
	CAMSAP3	ENST00000930508.1		c.166C>A	p.Leu56Met	missense	Exon 2 of 17	ENSP00000600567.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 7.10e-7 AC: 1 AN: 1408224 Hom.: 0 Cov.: 33 AF XY: 0.00000144 AC XY: 1 AN XY: 696636

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 31384

American (AMR) AF: 0.00 AC: 0 AN: 35912

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24100

East Asian (EAS) AF: 0.00 AC: 0 AN: 37064

South Asian (SAS) AF: 0.00 AC: 0 AN: 79592

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52482

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5570

European-Non Finnish (NFE) AF: 9.22e-7 AC: 1 AN: 1084094

Other (OTH) AF: 0.00 AC: 0 AN: 58026

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 30

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.60
BayesDel_addAF	Benign	-0.064	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.036	D
MetaRNN	Uncertain	0.58	D
MetaSVM	Benign	-0.83	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		2.0
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.21
Sift	Uncertain	0.0040	D
Sift4G	Benign	0.16	T
Polyphen		0.97	D
Vest4		0.56
MutPred		0.56		Loss of catalytic residue at L56 (P = 0.0031)
MVP		0.41
MPC		1.6
ClinPred		0.92	D
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.36
gMVP		0.58
Mutation Taster		=42/58	disease causing

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

Other links and lift over

hg19: chr19-7670129;