Variant 11-60842281-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

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

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:

CCDC86-AS1 (HGNC:):

CCDC86-AS1 links:

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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=0.12227422).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC86	NM_024098.4 linkuse as main transcript	c.157C>T	p.Arg53Trp	missense_variant	1/4	ENST00000227520.10	NP_077003.1	Q9H6F5-1
CCDC86-AS1	NR_182293.1 linkuse as main transcript	n.317-301G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CCDC86	ENST00000227520.10 linkuse as main transcript	c.157C>T	p.Arg53Trp	missense_variant	1/4	1	NM_024098.4	ENSP00000227520.5	Q9H6F5-1
CCDC86	ENST00000535217.1 linkuse as main transcript	n.136C>T		non_coding_transcript_exon_variant	1/5	5		ENSP00000442111.1	H0YG79
CCDC86-AS1	ENST00000538705.1 linkuse as main transcript	n.317-301G>A		intron_variant		3
ENSG00000255959	ENST00000539897.1 linkuse as main transcript	n.349+336G>A		intron_variant		4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000202

AC:

AN:

246974

Hom.:

AF XY:

0.0000224

AC XY:

AN XY:

134222

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 SAS exome

AF:

0.0000653

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

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000135

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000675

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000330

AC:

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

Sep 26, 2024

The c.157C>T (p.R53W) alteration is located in exon 1 (coding exon 1) of the CCDC86 gene. This alteration results from a C to T substitution at nucleotide position 157, causing the arginine (R) at amino acid position 53 to be replaced by a tryptophan (W). 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

0.095

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.49

CADD

Benign

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

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

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.12

gMVP

0.083

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