chr19-7606513-C-A

Variant names:

• chr19-7606513-C-A
• rs751813834
• NM_020902.2:c.563C>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_020902.2(CAMSAP3):​c.563C>A​(p.Ala188Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000167 in 1,554,334 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A188G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: CAMSAP3 NM_020902.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.929
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.26178664).
• BS2: High AC in GnomAdExome4 at 23 AD gene.

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.563C>A	p.Ala188Glu	missense	Exon 4 of 17	NP_065953.1	Q9P1Y5-1
	CAMSAP3	NM_001080429.3		c.563C>A	p.Ala188Glu	missense	Exon 4 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.563C>A	p.Ala188Glu	missense	Exon 4 of 17	ENSP00000160298.3	Q9P1Y5-1
	CAMSAP3	ENST00000446248.4	TSL:1	c.563C>A	p.Ala188Glu	missense	Exon 4 of 19	ENSP00000416797.1	Q9P1Y5-2
	CAMSAP3	ENST00000930508.1		c.563C>A	p.Ala188Glu	missense	Exon 4 of 17	ENSP00000600567.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152170 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

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: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000251 AC: 4 AN: 159578 AF XY: 0.0000343

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000570

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000164 AC: 23 AN: 1402164 Hom.: 0 Cov.: 35 AF XY: 0.0000202 AC XY: 14 AN XY: 694114

African (AFR) AF: 0.0000311 AC: 1 AN: 32130

American (AMR) AF: 0.00 AC: 0 AN: 36850

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25236

East Asian (EAS) AF: 0.00 AC: 0 AN: 36490

South Asian (SAS) AF: 0.00 AC: 0 AN: 81274

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35966

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4906

European-Non Finnish (NFE) AF: 0.0000183 AC: 20 AN: 1090740

Other (OTH) AF: 0.0000341 AC: 2 AN: 58572

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152170 Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 2 AN XY: 74334

African (AFR) AF: 0.00 AC: 0 AN: 41452

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68014

Other (OTH) AF: 0.00 AC: 0 AN: 2082

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0061	T
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.051
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.77	N
PhyloP100		0.93
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	0.33	N
REVEL	Benign	0.16
Sift	Benign	0.072	T
Sift4G	Benign	1.0	T
Polyphen		0.37	B
Vest4		0.59
MutPred		0.27		Loss of helix (P = 0.079)
MVP		0.41
MPC		1.7
ClinPred		0.27	T
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.22
gMVP		0.28
Mutation Taster		=90/10	polymorphism

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

dbSNP: rs751813834; hg19: chr19-7671399;