NM_015447.4:c.4527C>T

Variant names:

• chr9-135811591-G-A
• rs147212718
• NM_015447.4:c.4527C>T

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.4527C>T​(p.Ala1509Ala) variant causes a synonymous change. The variant allele was found at a frequency of 0.00000208 in 1,440,296 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A1509A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: CAMSAP1 NM_015447.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.56
• 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 (BayesDel_noAF=-0.33).

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.4527C>T	p.Ala1509Ala	synonymous	Exon 17 of 17	NP_056262.3	Q5T5Y3-1
	CAMSAP1	NM_001437279.1		c.4560C>T	p.Ala1520Ala	synonymous	Exon 18 of 18	NP_001424208.1
	CAMSAP1	NM_001437280.1		c.4095C>T	p.Ala1365Ala	synonymous	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.4527C>T	p.Ala1509Ala	synonymous	Exon 17 of 17	ENSP00000374183.4	Q5T5Y3-1
	CAMSAP1	ENST00000312405.10	TSL:1	c.3693C>T	p.Ala1231Ala	synonymous	Exon 15 of 15	ENSP00000312463.6	Q5T5Y3-2
	CAMSAP1	ENST00000409386.3	TSL:5	c.4560C>T	p.Ala1520Ala	synonymous	Exon 18 of 18	ENSP00000386420.3	Q5T5Y3-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000208 AC: 3 AN: 1440296 Hom.: 0 Cov.: 30 AF XY: 0.00000280 AC XY: 2 AN XY: 714278

African (AFR) AF: 0.00 AC: 0 AN: 33026

American (AMR) AF: 0.00 AC: 0 AN: 41240

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25704

East Asian (EAS) AF: 0.00 AC: 0 AN: 38844

South Asian (SAS) AF: 0.00 AC: 0 AN: 82926

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52098

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 0.00000272 AC: 3 AN: 1101054

Other (OTH) AF: 0.00 AC: 0 AN: 59654

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	9.1
DANN	Benign	0.70
PhyloP100		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs147212718; hg19: chr9-138703437;