11-788279-C-T

Variant summary

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

The NM_016564.4(CEND1):​c.298G>A​(p.Gly100Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,612,916 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 (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

CEND1
NM_016564.4 missense

Scores

1
5
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.152
Variant links:
Genes affected
CEND1 (HGNC:24153): (cell cycle exit and neuronal differentiation 1) The protein encoded by this gene is a neuron-specific protein. The similar protein in pig enhances neuroblastoma cell differentiation in vitro and may be involved in neuronal differentiation in vivo. Multiple pseudogenes have been reported for this gene. [provided by RefSeq, Jul 2008]

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=0.2399027).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CEND1NM_016564.4 linkc.298G>A p.Gly100Arg missense_variant Exon 2 of 2 ENST00000330106.5 NP_057648.2 Q8N111

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CEND1ENST00000330106.5 linkc.298G>A p.Gly100Arg missense_variant Exon 2 of 2 1 NM_016564.4 ENSP00000328336.4 Q8N111
CEND1ENST00000524587.1 linkn.371G>A non_coding_transcript_exon_variant Exon 2 of 2 3

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152172
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000204
AC:
5
AN:
245502
Hom.:
0
AF XY:
0.0000299
AC XY:
4
AN XY:
133750
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000291
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000165
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000908
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000123
AC:
18
AN:
1460744
Hom.:
0
Cov.:
31
AF XY:
0.0000124
AC XY:
9
AN XY:
726680
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000151
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000810
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152172
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74332
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
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
Bravo
AF:
0.0000113
ExAC
AF:
0.0000248
AC:
3

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Sep 04, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.298G>A (p.G100R) alteration is located in exon 2 (coding exon 1) of the CEND1 gene. This alteration results from a G to A substitution at nucleotide position 298, causing the glycine (G) at amino acid position 100 to be replaced by an arginine (R). 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
Uncertain
0.51
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.30
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.62
D
Eigen
Benign
0.061
Eigen_PC
Benign
-0.031
FATHMM_MKL
Benign
0.10
N
LIST_S2
Benign
0.73
T
M_CAP
Benign
0.026
D
MetaRNN
Benign
0.24
T
MetaSVM
Benign
-0.94
T
MutationAssessor
Benign
1.8
L
PrimateAI
Uncertain
0.76
T
PROVEAN
Pathogenic
-5.7
D
REVEL
Benign
0.12
Sift
Uncertain
0.0070
D
Sift4G
Benign
0.17
T
Polyphen
1.0
D
Vest4
0.17
MutPred
0.19
Gain of solvent accessibility (P = 0.0674);
MVP
0.082
MPC
0.67
ClinPred
0.74
D
GERP RS
4.8
Varity_R
0.48
gMVP
0.13

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: rs762710448; hg19: chr11-788279; COSMIC: COSV57192414; COSMIC: COSV57192414; API