Variant 17-56950604-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_004645.3(COIL):c.638A>G(p.Asn213Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000567 in 1,614,226 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00059 ( 1 hom. )

Consequence

COIL
NM_004645.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.571

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]

COIL links:

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=0.016108066).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COIL	NM_004645.3 linkuse as main transcript	c.638A>G	p.Asn213Ser	missense_variant	2/7	ENST00000240316.5	NP_004636.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COIL	ENST00000240316.5 linkuse as main transcript	c.638A>G	p.Asn213Ser	missense_variant	2/7	1	NM_004645.3	ENSP00000240316	P1

Frequencies

GnomAD3 genomes

AF:

0.000322

AC:

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000588

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000346

AC:

AN:

251466

Hom.:

AF XY:

0.000405

AC XY:

AN XY:

135908

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000794

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000668

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000592

AC:

866

AN:

1461870

Hom.:

Cov.:

AF XY:

0.000580

AC XY:

422

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000650

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000735

Gnomad4 OTH exome

AF:

0.000397

GnomAD4 genome

AF:

0.000322

AC:

AN:

152356

Hom.:

Cov.:

AF XY:

0.000268

AC XY:

AN XY:

74512

show subpopulations

Gnomad4 AFR

AF:

0.0000962

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000588

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000487

Hom.:

Bravo

AF:

0.000306

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00116

AC:

ExAC

AF:

0.000354

AC:

EpiCase

AF:

0.000763

EpiControl

AF:

0.000711

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 submitter

clinical testing

Ambry Genetics

Feb 23, 2023

The c.638A>G (p.N213S) alteration is located in exon 2 (coding exon 2) of the COIL gene. This alteration results from a A to G substitution at nucleotide position 638, causing the asparagine (N) at amino acid position 213 to be replaced by a serine (S). 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

0.063

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.63

CADD

Benign

0.0090

DANN

Benign

0.50

DEOGEN2

Benign

0.070

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.062

LIST_S2

Benign

0.32

M_CAP

Benign

0.015

MetaRNN

Benign

0.016

MetaSVM

Benign

-0.88

MutationAssessor

Benign

0.14

MutationTaster

Benign

1.0

PrimateAI

Benign

0.25

PROVEAN

Benign

0.080

REVEL

Benign

0.095

Sift

Benign

0.82

Sift4G

Benign

0.96

Polyphen

0.0020

Vest4

0.031

MVP

0.32

MPC

0.053

ClinPred

0.026

GERP RS

-0.80

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.030

gMVP

0.036

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