Genetic Variant NM_198489.3:c.205T>A (chr11-118998514-T-A) – ACMG Classification: Uncertain_significance (5 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PM2PP2PP3_Moderate

The NM_198489.3(CENATAC):c.205T>A(p.Cys69Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,458,696 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

CENATAC
NM_198489.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.53

Publications

0 publications found

Variant links:

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

CENATAC links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CENATAC	NM_198489.3	MANE Select	c.205T>A	p.Cys69Ser	missense	Exon 2 of 11	NP_940891.1	Q86UT8
CENATAC	NR_104049.2		n.265T>A		non_coding_transcript_exon	Exon 2 of 11
CENATAC	NR_104050.2		n.265T>A		non_coding_transcript_exon	Exon 2 of 11

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1458696

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725404

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33444

American (AMR)

AF:

0.00

AC:

AN:

44238

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25988

East Asian (EAS)

AF:

0.00

AC:

AN:

39622

South Asian (SAS)

AF:

0.00

AC:

AN:

85664

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53056

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1110686

Other (OTH)

AF:

0.00

AC:

AN:

60236

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.95

BayesDel_addAF

Pathogenic

0.38

BayesDel_noAF

Pathogenic

0.30

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.35

Eigen

Uncertain

0.66

Eigen_PC

Uncertain

0.64

FATHMM_MKL

Uncertain

0.77

M_CAP

Benign

0.061

MetaRNN

Pathogenic

0.90

MetaSVM

Uncertain

0.14

MutationAssessor

Uncertain

2.4

PhyloP100

4.5

PrimateAI

Uncertain

0.60

PROVEAN

Pathogenic

-6.2

REVEL

Pathogenic

0.84

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.010

Polyphen

1.0

Vest4

0.88

MutPred

0.70

Loss of sheet (P = 0.0817)

MVP

0.93

MPC

0.47

ClinPred

0.99

GERP RS

5.1

PromoterAI

-0.025

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.89

gMVP

0.84

Mutation Taster

=35/65

disease causing

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over