Genetic Variant CENATAC:p.Arg11Cys (chr11-118998228-C-T) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_198489.3(CENATAC):c.31C>T(p.Arg11Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000489 in 1,432,448 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: 0.0000049 ( 0 hom. )

Consequence

CENATAC
NM_198489.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.77

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 links:

CENATAC-DT (HGNC:54215): (CENATAC divergent transcript)

CENATAC-DT links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.801

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CENATAC	NM_198489.3 link	c.31C>T	p.Arg11Cys	missense_variant	Exon 1 of 11	ENST00000334418.6	NP_940891.1	Q86UT8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CENATAC	ENST00000334418.6 link	c.31C>T	p.Arg11Cys	missense_variant	Exon 1 of 11	1	NM_198489.3	ENSP00000334767.1		Q86UT8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000510

AC:

AN:

196192

Hom.:

AF XY:

0.00

AC XY:

AN XY:

106136

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000111

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000489

AC:

AN:

1432448

Hom.:

Cov.:

AF XY:

0.00000423

AC XY:

AN XY:

710004

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000118

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000273

Gnomad4 OTH exome

AF:

0.0000169

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000831

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 09, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.31C>T (p.R11C) alteration is located in exon 1 (coding exon 1) of the CCDC84 gene. This alteration results from a C to T substitution at nucleotide position 31, causing the arginine (R) at amino acid position 11 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.31

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

-0.080

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.20

Eigen

Uncertain

0.61

Eigen_PC

Uncertain

0.60

FATHMM_MKL

Uncertain

0.78

M_CAP

Benign

0.025

MetaRNN

Pathogenic

0.80

MetaSVM

Benign

-0.61

MutationAssessor

Uncertain

2.2

PrimateAI

Pathogenic

0.79

PROVEAN

Pathogenic

-4.6

REVEL

Uncertain

0.30

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0040

Polyphen

1.0

Vest4

0.63

MutPred

0.71

Loss of MoRF binding (P = 0.007);

MVP

0.70

MPC

0.49

ClinPred

1.0

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.53

gMVP

0.66

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over