2-65069601-T-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_015147.3(CEP68):ā€‹c.157T>Gā€‹(p.Ser53Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000285 in 1,613,840 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000059 ( 0 hom., cov: 32)
Exomes š‘“: 0.000025 ( 2 hom. )

Consequence

CEP68
NM_015147.3 missense

Scores

1
2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.86
Variant links:
Genes affected
CEP68 (HGNC:29076): (centrosomal protein 68) Enables protein domain specific binding activity and protein kinase binding activity. Involved in centriole-centriole cohesion and protein localization to organelle. Located in several cellular components, including centriolar satellite; cytosol; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.096884966).
BS2
High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CEP68NM_015147.3 linkuse as main transcriptc.157T>G p.Ser53Ala missense_variant 2/7 ENST00000377990.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CEP68ENST00000377990.7 linkuse as main transcriptc.157T>G p.Ser53Ala missense_variant 2/71 NM_015147.3 P2Q76N32-1

Frequencies

GnomAD3 genomes
AF:
0.0000592
AC:
9
AN:
152138
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000458
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:
0.000957
GnomAD3 exomes
AF:
0.000116
AC:
29
AN:
250696
Hom.:
2
AF XY:
0.0000959
AC XY:
13
AN XY:
135586
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000839
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000253
AC:
37
AN:
1461702
Hom.:
2
Cov.:
30
AF XY:
0.0000206
AC XY:
15
AN XY:
727156
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000827
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000592
AC:
9
AN:
152138
Hom.:
0
Cov.:
32
AF XY:
0.0000807
AC XY:
6
AN XY:
74310
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000458
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:
0.000957
Bravo
AF:
0.000166
ExAC
AF:
0.0000494
AC:
6

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJul 12, 2022The c.157T>G (p.S53A) alteration is located in exon 2 (coding exon 1) of the CEP68 gene. This alteration results from a T to G substitution at nucleotide position 157, causing the serine (S) at amino acid position 53 to be replaced by an alanine (A). 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
0.11
BayesDel_addAF
Benign
-0.37
T
BayesDel_noAF
Benign
-0.38
CADD
Benign
19
DANN
Uncertain
1.0
DEOGEN2
Benign
0.0092
T;.
Eigen
Uncertain
0.19
Eigen_PC
Benign
0.13
FATHMM_MKL
Benign
0.55
D
LIST_S2
Benign
0.49
T;T
M_CAP
Benign
0.0060
T
MetaRNN
Benign
0.097
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.8
L;L
MutationTaster
Benign
1.0
D;N;N;N
PrimateAI
Benign
0.40
T
PROVEAN
Benign
-0.89
N;N
REVEL
Benign
0.076
Sift
Pathogenic
0.0
D;D
Sift4G
Benign
0.25
T;T
Polyphen
1.0
D;D
Vest4
0.21
MutPred
0.18
Loss of glycosylation at S53 (P = 0.0681);Loss of glycosylation at S53 (P = 0.0681);
MVP
0.38
MPC
0.28
ClinPred
0.23
T
GERP RS
4.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.31
gMVP
0.094

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: rs766769339; hg19: chr2-65296735; API