Genetic Variant CCDC86:p.Arg53Trp (chr11-60842281-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024098.4(CCDC86):c.157C>T(p.Arg53Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000144 in 1,461,216 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

CCDC86
NM_024098.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.252

Publications

1 publications found

Variant links:

Genes affected

CCDC86 (HGNC:28359): (coiled-coil domain containing 86) Enables RNA binding activity. Located in chromosome; nucleolus; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

CCDC86 links:

ENSG00000255959 (HGNC:):

ENSG00000255959 links:

CCDC86-AS1 (HGNC:56314): (CCDC86 antisense RNA 1)

CCDC86-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12227422).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024098.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC86	NM_024098.4	MANE Select	c.157C>T	p.Arg53Trp	missense	Exon 1 of 4	NP_077003.1	Q9H6F5-1
	CCDC86-AS1	NR_182293.1		n.317-301G>A		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCDC86	ENST00000227520.10	TSL:1 MANE Select	c.157C>T	p.Arg53Trp	missense	Exon 1 of 4	ENSP00000227520.5	Q9H6F5-1
CCDC86	ENST00000535217.1	TSL:5	n.136C>T		non_coding_transcript_exon	Exon 1 of 5	ENSP00000442111.1	H0YG79
ENSG00000255959	ENST00000753860.1		n.380G>A		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000202

AC:

AN:

246974

AF XY:

0.0000224

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000545

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000182

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000144

AC:

AN:

1461216

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

726936

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.0000224

AC:

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000348

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52876

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000135

AC:

AN:

1111918

Other (OTH)

AF:

0.0000166

AC:

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000675

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000330

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.056

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.027

LIST_S2

Benign

0.54

M_CAP

Benign

0.0076

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.90

PhyloP100

0.25

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.99

REVEL

Benign

0.079

Sift

Uncertain

0.026

Sift4G

Uncertain

0.021

Polyphen

0.95

Vest4

0.15

MutPred

0.23

Gain of glycosylation at P49 (P = 0.1124)

MVP

0.61

MPC

0.64

ClinPred

0.28

GERP RS

2.9

PromoterAI

-0.0092

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.12

gMVP

0.083

Mutation Taster

=98/2

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over