17-56950187-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_004645.3(COIL):​c.1055G>A​(p.Arg352His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000929 in 1,613,838 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000096 ( 0 hom. )

Consequence

COIL
NM_004645.3 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.394
Variant links:
Genes affected
COIL (HGNC:2184): (coilin) The protein encoded by this gene is an integral component of Cajal bodies (also called coiled bodies). Cajal bodies are nuclear suborganelles of varying number and composition that are involved in the post-transcriptional modification of small nuclear and small nucleolar RNAs. The N-terminus of the coilin protein directs its self-oligomerization while the C-terminus influences the number of nuclear bodies assembled per cell. Differential methylation and phosphorylation of coilin likely influences its localization among nuclear bodies and the composition and assembly of Cajal bodies. This gene has pseudogenes on chromosome 4 and chromosome 14. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.048003167).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
COILNM_004645.3 linkuse as main transcriptc.1055G>A p.Arg352His missense_variant 2/7 ENST00000240316.5 NP_004636.1 P38432

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
COILENST00000240316.5 linkuse as main transcriptc.1055G>A p.Arg352His missense_variant 2/71 NM_004645.3 ENSP00000240316.4 P38432

Frequencies

GnomAD3 genomes
AF:
0.0000657
AC:
10
AN:
152126
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.000865
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000882
Gnomad OTH
AF:
0.000480
GnomAD3 exomes
AF:
0.0000955
AC:
24
AN:
251302
Hom.:
0
AF XY:
0.000133
AC XY:
18
AN XY:
135838
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00139
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000880
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000958
AC:
140
AN:
1461712
Hom.:
0
Cov.:
34
AF XY:
0.000113
AC XY:
82
AN XY:
727166
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00119
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000899
Gnomad4 OTH exome
AF:
0.000116
GnomAD4 genome
AF:
0.0000657
AC:
10
AN:
152126
Hom.:
0
Cov.:
32
AF XY:
0.0000807
AC XY:
6
AN XY:
74306
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.000865
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000882
Gnomad4 OTH
AF:
0.000480
Alfa
AF:
0.000304
Hom.:
0
Bravo
AF:
0.0000680
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.00
AC:
0
ExAC
AF:
0.000115
AC:
14
EpiCase
AF:
0.00
EpiControl
AF:
0.000178

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 GeneticsOct 18, 2021The c.1055G>A (p.R352H) alteration is located in exon 2 (coding exon 2) of the COIL gene. This alteration results from a G to A substitution at nucleotide position 1055, causing the arginine (R) at amino acid position 352 to be replaced by a histidine (H). 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
0.071
BayesDel_addAF
Benign
-0.31
T
BayesDel_noAF
Benign
-0.47
CADD
Benign
20
DANN
Uncertain
0.99
DEOGEN2
Benign
0.058
T
Eigen
Benign
-0.32
Eigen_PC
Benign
-0.32
FATHMM_MKL
Benign
0.39
N
LIST_S2
Benign
0.67
T
M_CAP
Benign
0.0021
T
MetaRNN
Benign
0.048
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.34
N
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.27
T
PROVEAN
Benign
-0.080
N
REVEL
Benign
0.12
Sift
Benign
0.078
T
Sift4G
Benign
0.46
T
Polyphen
0.82
P
Vest4
0.10
MVP
0.48
MPC
0.12
ClinPred
0.10
T
GERP RS
5.8
Varity_R
0.17
gMVP
0.081

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: rs140691052; hg19: chr17-55027548; API