rs1553238311

Variant names:

• chr1-7661860-AG-A
• rs1553238311
• NM_015215.4:c.800delG

Variant summary

Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_015215.4(CAMTA1):​c.800delG​(p.Ser267ThrfsTer123) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CAMTA1 NM_015215.4 frameshift
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 2.47
• Publications: 0 publications found

Genes affected

CAMTA1 (HGNC:18806): (calmodulin binding transcription activator 1) The protein encoded by this gene contains a CG1 DNA-binding domain, a transcription factor immunoglobulin domain, ankyrin repeats, and calmodulin-binding IQ motifs. The encoded protein is thought to be a transcription factor and may be a tumor suppressor. However, a translocation event is sometimes observed between this gene and the WWTR1 gene, with the resulting WWTR1-CAMTA1 oncoprotein leading to epithelioid hemangioendothelioma, a malignant vascular cancer. [provided by RefSeq, Mar 2017]

CAMTA1 Gene-Disease associations (from GenCC):

• cerebellar dysfunction with variable cognitive and behavioral abnormalities

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, Orphanet, ClinGen

ACMG classification

Our verdict: Pathogenic. The variant received 12 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 1-7661860-AG-A is Pathogenic according to our data. Variant chr1-7661860-AG-A is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 559860.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015215.4. 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
	CAMTA1	NM_015215.4	MANE Select	c.800delG	p.Ser267ThrfsTer123	frameshift	Exon 8 of 23	NP_056030.1	Q9Y6Y1-1
	CAMTA1	NM_001349608.2		c.710delG	p.Ser237ThrfsTer123	frameshift	Exon 7 of 22	NP_001336537.1
	CAMTA1	NM_001349609.2		c.800delG	p.Ser267ThrfsTer123	frameshift	Exon 8 of 23	NP_001336538.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAMTA1	ENST00000303635.12	TSL:1 MANE Select	c.800delG	p.Ser267ThrfsTer123	frameshift	Exon 8 of 23	ENSP00000306522.6	Q9Y6Y1-1
	CAMTA1	ENST00000476864.2	TSL:1	c.800delG	p.Ser267ThrfsTer123	frameshift	Exon 8 of 22	ENSP00000452319.2	A0A0C4DGL0
	CAMTA1	ENST00000700415.1		c.710delG	p.Ser237ThrfsTer123	frameshift	Exon 7 of 23	ENSP00000514979.1	A0A8V8TQ65

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely pathogenic

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	-	-	Cerebellar dysfunction with variable cognitive and behavioral abnormalities (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.5

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1553238311;

hg19: chr1-7721920;