9-135811608-G-T

Variant names:

• chr9-135811608-G-T
• NM_015447.4:c.4510C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015447.4(CAMSAP1):​c.4510C>A​(p.Leu1504Met) 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. 14/22 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)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CAMSAP1 NM_015447.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.87
• Publications: 0 publications found

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]

CAMSAP1 Gene-Disease associations (from GenCC):

• cortical dysplasia, complex, with other brain malformations 12

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19535494).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015447.4. 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
	CAMSAP1	NM_015447.4	MANE Select	c.4510C>A	p.Leu1504Met	missense	Exon 17 of 17	NP_056262.3	Q5T5Y3-1
	CAMSAP1	NM_001437279.1		c.4543C>A	p.Leu1515Met	missense	Exon 18 of 18	NP_001424208.1
	CAMSAP1	NM_001437280.1		c.4078C>A	p.Leu1360Met	missense	Exon 16 of 16	NP_001424209.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAMSAP1	ENST00000389532.9	TSL:5 MANE Select	c.4510C>A	p.Leu1504Met	missense	Exon 17 of 17	ENSP00000374183.4	Q5T5Y3-1
	CAMSAP1	ENST00000312405.10	TSL:1	c.3676C>A	p.Leu1226Met	missense	Exon 15 of 15	ENSP00000312463.6	Q5T5Y3-2
	CAMSAP1	ENST00000409386.3	TSL:5	c.4543C>A	p.Leu1515Met	missense	Exon 18 of 18	ENSP00000386420.3	Q5T5Y3-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1430870 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 708598

African (AFR) AF: 0.00 AC: 0 AN: 32728

American (AMR) AF: 0.00 AC: 0 AN: 39762

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25548

East Asian (EAS) AF: 0.00 AC: 0 AN: 38280

South Asian (SAS) AF: 0.00 AC: 0 AN: 81836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51548

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5742

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1096108

Other (OTH) AF: 0.00 AC: 0 AN: 59318

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Uncertain	23
DANN	Benign	0.30
DEOGEN2	Benign	0.039	T
Eigen	Benign	0.13
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.90	L
PhyloP100		1.9
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	0.57	N
REVEL	Benign	0.13
Sift	Benign	0.91	T
Sift4G	Benign	1.0	T
Polyphen		0.99	D
Vest4		0.33
MutPred		0.57		Gain of disorder (P = 0.1025)
MVP		0.35
MPC		0.90
ClinPred		0.40	T
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.16
gMVP		0.54
Mutation Taster		=80/20	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: chr9-138703454;