CENATAC p.Cys69Ser

Variant names:

• chr11-118998515-G-C
• NM_198489.3:c.206G>C
• CENATAC p.Cys69Ser

Your query was ambiguous. Multiple possible variants found:

• chr11-118998515-G-C
• chr11-118998514-T-A
• chr11-118998515-GC-CT
• chr11-118998515-GC-CA
• chr11-118998515-GC-CG
• chr11-118998514-TGC-AGT

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PM2 PP2 PP3_Moderate

The NM_198489.3(CENATAC):​c.206G>C​(p.Cys69Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 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 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• 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.
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.901

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.206G>C	p.Cys69Ser	missense	Exon 2 of 11	NP_940891.1	Q86UT8
	CENATAC	NR_104049.2		n.266G>C		non_coding_transcript_exon	Exon 2 of 11
	CENATAC	NR_104050.2		n.266G>C		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.206G>C	p.Cys69Ser	missense	Exon 2 of 11	ENSP00000334767.1	Q86UT8
	CENATAC	ENST00000526463.5	TSL:1	n.206G>C		non_coding_transcript_exon	Exon 2 of 11	ENSP00000436340.1	E9PPT8
	CENATAC	ENST00000532132.5	TSL:1	n.206G>C		non_coding_transcript_exon	Exon 2 of 11	ENSP00000431889.1	E9PJ16

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Pathogenic	0.38	D
BayesDel_noAF	Pathogenic	0.31
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Benign	0.35	T
Eigen	Pathogenic	0.75
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Uncertain	0.83	D
M_CAP	Benign	0.038	D
MetaRNN	Pathogenic	0.90	D
MetaSVM	Uncertain	0.17	D
MutationAssessor	Uncertain	2.4	M
PhyloP100		5.6
PrimateAI	Uncertain	0.60	T
PROVEAN	Pathogenic	-6.2	D
REVEL	Pathogenic	0.80
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.010	D
PromoterAI		0.025	Neutral
Varity_R		0.86
gMVP		0.84
Mutation Taster		=43/57	disease causing

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

hg19: chr11-118869225;