1-6825072-TATTGTTTTCTTCTTTGTAG-T

Variant names:

• chr1-6825072-TATTGTTTTCTTCTTTGTAG-T
• NM_015215.4:c.116-17_117delTGTTTTCTTCTTTGTAGAT

Variant summary

Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PVS1 PP5_Moderate

The NM_015215.4(CAMTA1):​c.116-17_117delTGTTTTCTTCTTTGTAGAT​(p.Asp39fs) variant causes a frameshift, splice acceptor, splice region, intron change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CAMTA1 NM_015215.4 frameshift, splice_acceptor, splice_region, intron
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 3.87
• 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: ClinGen, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, Orphanet

ACMG classification

Our verdict: Pathogenic. The variant received 10 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PP5: Variant 1-6825072-TATTGTTTTCTTCTTTGTAG-T is Pathogenic according to our data. Variant chr1-6825072-TATTGTTTTCTTCTTTGTAG-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 3893251.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAMTA1	NM_015215.4	c.116-17_117delTGTTTTCTTCTTTGTAGAT	p.Asp39fs	frameshift_variant, splice_acceptor_variant, splice_region_variant, intron_variant	Exon 3 of 23	ENST00000303635.12	NP_056030.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAMTA1	ENST00000303635.12	c.116-19_116-1delATTGTTTTCTTCTTTGTAG		splice_acceptor_variant, splice_region_variant, intron_variant	Intron 2 of 22	1	NM_015215.4	ENSP00000306522.6

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Cerebellar dysfunction with variable cognitive and behavioral abnormalities Pathogenic:1

Oct 24, 2023

Illumina Laboratory Services, Illumina

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The CAMTA1 c.116-17_117del variant results in the deletion of 19 nucleotides in the splice region of intron 2, including the consensus splice acceptor site, which may result in splicing defects. To our knowledge, this variant has not been reported in the peer-reviewed literature. The c.116-17_117del variant is not observed in version 2.1.1 or version 3.1.2 of the Genome Aggregation Database. Based on the available evidence, the c.116-17_117del variant is classified as likely pathogenic for cerebellar dysfunction with variable cognitive and behavioral abnormalities. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.9

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr1-6885132;