NM_198489.3:c.309C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_198489.3(CENATAC):​c.309C>G​(p.Asn103Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000316 in 1,613,950 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N103S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000099 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

CENATAC
NM_198489.3 missense

Scores

1
5
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.00700
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.23451126).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CENATACNM_198489.3 linkc.309C>G p.Asn103Lys missense_variant Exon 3 of 11 ENST00000334418.6 NP_940891.1 Q86UT8
CENATACNR_104049.2 linkn.369C>G non_coding_transcript_exon_variant Exon 3 of 11
CENATACNR_104050.2 linkn.369C>G non_coding_transcript_exon_variant Exon 3 of 11
CENATACNR_104051.2 linkn.369C>G non_coding_transcript_exon_variant Exon 3 of 11

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CENATACENST00000334418.6 linkc.309C>G p.Asn103Lys missense_variant Exon 3 of 11 1 NM_198489.3 ENSP00000334767.1 Q86UT8

Frequencies

GnomAD3 genomes
AF:
0.0000986
AC:
15
AN:
152120
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000338
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000656
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000318
AC:
8
AN:
251486
Hom.:
0
AF XY:
0.0000294
AC XY:
4
AN XY:
135916
show subpopulations
Gnomad AFR exome
AF:
0.000308
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000264
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000246
AC:
36
AN:
1461830
Hom.:
0
Cov.:
30
AF XY:
0.0000124
AC XY:
9
AN XY:
727220
show subpopulations
Gnomad4 AFR exome
AF:
0.000508
Gnomad4 AMR exome
AF:
0.0000447
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000809
Gnomad4 OTH exome
AF:
0.000116
GnomAD4 genome
AF:
0.0000986
AC:
15
AN:
152120
Hom.:
0
Cov.:
32
AF XY:
0.0000673
AC XY:
5
AN XY:
74312
show subpopulations
Gnomad4 AFR
AF:
0.000338
Gnomad4 AMR
AF:
0.0000656
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000564
Hom.:
0
Bravo
AF:
0.000181
ESP6500AA
AF:
0.000682
AC:
3
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000412
AC:
5

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 22, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.309C>G (p.N103K) alteration is located in exon 3 (coding exon 3) of the CCDC84 gene. This alteration results from a C to G substitution at nucleotide position 309, causing the asparagine (N) at amino acid position 103 to be replaced by a lysine (K). 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
Pathogenic
0.61
BayesDel_addAF
Benign
-0.41
T
BayesDel_noAF
Benign
-0.52
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.0097
T
Eigen
Uncertain
0.24
Eigen_PC
Uncertain
0.23
FATHMM_MKL
Benign
0.11
N
M_CAP
Benign
0.010
T
MetaRNN
Benign
0.23
T
MetaSVM
Benign
-0.91
T
MutationAssessor
Uncertain
2.1
M
PrimateAI
Uncertain
0.68
T
PROVEAN
Benign
0.92
N
REVEL
Benign
0.13
Sift
Benign
0.16
T
Sift4G
Benign
0.36
T
Polyphen
1.0
D
Vest4
0.43
MutPred
0.27
Gain of methylation at N103 (P = 0.0073);
MVP
0.40
MPC
0.45
ClinPred
0.24
T
GERP RS
2.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.17
gMVP
0.29

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.

Other links and lift over

dbSNP: rs373436467; hg19: chr11-118869745; API