Variant chr11-60842564-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 ENST00000227520.10(CCDC86):c.440C>T(p.Pro147Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,460,846 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

CCDC86
ENST00000227520.10 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.245

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:56314): (CCDC86 antisense RNA 1)

CCDC86-AS1 links:

(HGNC:):

links:

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=0.13469842).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC86	NM_024098.4 linkuse as main transcript	c.440C>T	p.Pro147Leu	missense_variant	1/4	ENST00000227520.10	NP_077003.1
CCDC86-AS1	NR_182293.1 linkuse as main transcript	n.317-584G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC86	ENST00000227520.10 linkuse as main transcript	c.440C>T	p.Pro147Leu	missense_variant	1/4	1	NM_024098.4	ENSP00000227520	P1	Q9H6F5-1
CCDC86-AS1	ENST00000538705.1 linkuse as main transcript	n.317-584G>A		intron_variant, non_coding_transcript_variant		3
	ENST00000539897.1 linkuse as main transcript	n.349+53G>A		intron_variant, non_coding_transcript_variant		4
CCDC86	ENST00000535217.1 linkuse as main transcript	c.261-137C>T		intron_variant, NMD_transcript_variant		5		ENSP00000442111

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000403

AC:

AN:

248092

Hom.:

AF XY:

0.00000742

AC XY:

AN XY:

134778

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000896

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1460846

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

726706

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000540

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000312

Hom.:

Bravo

AF:

0.00000756

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

Nov 03, 2023

The c.440C>T (p.P147L) 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 440, causing the proline (P) at amino acid position 147 to be replaced by a leucine (L). 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

0.077

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.82

DEOGEN2

Benign

0.080

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.90

FATHMM_MKL

Benign

0.045

LIST_S2

Benign

0.40

M_CAP

Benign

0.031

MetaRNN

Benign

0.13

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.9

MutationTaster

Benign

0.97

PrimateAI

Benign

0.33

PROVEAN

Benign

-2.0

REVEL

Benign

0.084

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.031

Polyphen

0.098

Vest4

0.20

MutPred

0.39

Loss of glycosylation at T146 (P = 0.0631);

MVP

0.60

MPC

0.38

ClinPred

0.096

GERP RS

0.45

Varity_R

0.052

gMVP

0.061

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