19-7605262-C-T

Position:

• chr19-7605262-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_020902.2(CAMSAP3):​c.185C>T​(p.Thr62Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000688 in 1,452,722 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: 0.0000069 (0 hom.)
• Consequence: CAMSAP3 NM_020902.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.83

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 Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAMSAP3	NM_020902.2	c.185C>T	p.Thr62Ile	missense_variant	2/17	ENST00000160298.9	NP_065953.1
CAMSAP3	NM_001080429.3	c.185C>T	p.Thr62Ile	missense_variant	2/19		NP_001073898.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAMSAP3	ENST00000160298.9	c.185C>T	p.Thr62Ile	missense_variant	2/17	2	NM_020902.2	ENSP00000160298.3
CAMSAP3	ENST00000446248.4	c.185C>T	p.Thr62Ile	missense_variant	2/19	1		ENSP00000416797.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000688 AC: 10 AN: 1452722 Hom.: 0 Cov.: 33 AF XY: 0.00000969 AC XY: 7 AN XY: 722284

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: 0.00000813

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

Alfa AF: 0.0000470 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 14, 2024

The c.185C>T (p.T62I) alteration is located in exon 2 (coding exon 2) of the CAMSAP3 gene. This alteration results from a C to T substitution at nucleotide position 185, causing the threonine (T) at amino acid position 62 to be replaced by an isoleucine (I). 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	Pathogenic	0.63
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T;.
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.22
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Uncertain	0.87	D;D
M_CAP	Benign	0.039	D
MetaRNN	Uncertain	0.57	D;D
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.4	L;L
PrimateAI	Pathogenic	0.84	D
PROVEAN	Uncertain	-2.6	D;D
REVEL	Benign	0.10
Sift	Benign	0.28	T;T
Sift4G	Benign	0.070	T;T
Polyphen		1.0	D;D
Vest4		0.71
MutPred		0.33		Loss of disorder (P = 0.0714);Loss of disorder (P = 0.0714);
MVP		0.41
MPC		1.7
ClinPred		0.96	D
GERP RS		4.5
Varity_R		0.18
gMVP		0.40

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: rs2030151705; hg19: chr19-7670148;