11-118998514-TGC-AGT

Variant names:

• chr11-118998514-TGC-AGT
• NM_198489.3:c.205_207delTGCinsAGT
• CENATAC p.Cys69Ser

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP2

The NM_198489.3(CENATAC):​c.205_207delTGCinsAGT​(p.Cys69Ser) variant causes a missense 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 MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CENATAC NM_198489.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.64
• Publications: 0 publications found

Genes affected

CENATAC (HGNC:30460): (centrosomal AT-AC splicing factor) This gene encodes a protein thought to contain a coiled coil motif. No function has been determined for the encoded protein. A pseudogene of this gene is located on chromosome 20. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

CENATAC Gene-Disease associations (from GenCC):

• mosaic variegated aneuploidy syndrome 4

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP2: Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 1 curated pathogenic missense variants (we use a threshold of 10). The gene has 0 curated benign missense variants. Gene score misZ: 0.049395 (below the threshold of 3.09). Trascript score misZ: -0.8556 (below the threshold of 3.09). GenCC associations: The gene is linked to mosaic variegated aneuploidy syndrome 4.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198489.3. 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
	CENATAC	NM_198489.3	MANE Select	c.205_207delTGCinsAGT	p.Cys69Ser	missense	N/A	NP_940891.1	Q86UT8
	CENATAC	NR_104049.2		n.265_267delTGCinsAGT		non_coding_transcript_exon	Exon 2 of 11
	CENATAC	NR_104050.2		n.265_267delTGCinsAGT		non_coding_transcript_exon	Exon 2 of 11

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CENATAC	ENST00000334418.6	TSL:1 MANE Select	c.205_207delTGCinsAGT	p.Cys69Ser	missense	N/A	ENSP00000334767.1	Q86UT8
	CENATAC	ENST00000526463.5	TSL:1	n.205_207delTGCinsAGT		non_coding_transcript_exon	Exon 2 of 11	ENSP00000436340.1	E9PPT8
	CENATAC	ENST00000532132.5	TSL:1	n.205_207delTGCinsAGT		non_coding_transcript_exon	Exon 2 of 11	ENSP00000431889.1	E9PJ16

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.6

Splicing

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

hg19: chr11-118869224;