2-218580599-GATCT-G

Variant names:

• chr2-218580599-GATCT-G
• NM_005444.3:c.67_70delTATC

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005444.3(CNOT9):​c.67_70delTATC​(p.Tyr23SerfsTer19) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CNOT9 NM_005444.3 frameshift
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.30

Genes affected

CNOT9 (HGNC:10445): (CCR4-NOT transcription complex subunit 9) This gene encodes a member of the highly conserved RCD1 protein family. The encoded protein is a transcriptional cofactor and a core protein of the CCR4-NOT complex. It may be involved in signal transduction as well as retinoic acid-regulated cell differentiation and development. Alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Oct 2012]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNOT9	NM_005444.3	c.67_70delTATC	p.Tyr23SerfsTer19	frameshift_variant	Exon 2 of 8	ENST00000273064.11	NP_005435.1
CNOT9	NM_001271634.2	c.67_70delTATC	p.Tyr23SerfsTer19	frameshift_variant	Exon 2 of 9		NP_001258563.1
CNOT9	NM_001271635.2	c.67_70delTATC	p.Tyr23SerfsTer19	frameshift_variant	Exon 2 of 8		NP_001258564.1
CNOT9	NR_073390.2	n.183_186delTATC		non_coding_transcript_exon_variant	Exon 2 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNOT9	ENST00000273064.11	c.67_70delTATC	p.Tyr23SerfsTer19	frameshift_variant	Exon 2 of 8	1	NM_005444.3	ENSP00000273064.6

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: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Aug 17, 2024

GeneDx

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Not observed at significant frequency in large population cohorts (gnomAD); Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is not an established mechanism of disease; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-219445322;