Variant 11-85915460-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_001286159.2(CCDC83):c.836C>T(p.Pro279Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,184 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

CCDC83
NM_001286159.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.147

Variant links:

Genes affected

CCDC83 (HGNC:28535): (coiled-coil domain containing 83)

CCDC83 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=0.089741915).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC83	NM_001286159.2 linkuse as main transcript	c.836C>T	p.Pro279Leu	missense_variant	9/11	ENST00000342404.8	NP_001273088.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC83	ENST00000342404.8 linkuse as main transcript	c.836C>T	p.Pro279Leu	missense_variant	9/11	1	NM_001286159.2	ENSP00000344512	P1	Q8IWF9-1
CCDC83	ENST00000526729.1 linkuse as main transcript	c.554C>T	p.Pro185Leu	missense_variant	6/8	1		ENSP00000434373
CCDC83	ENST00000280245.8 linkuse as main transcript	c.929C>T	p.Pro310Leu	missense_variant	10/12	2		ENSP00000280245		Q8IWF9-2
CCDC83	ENST00000529676.2 linkuse as main transcript			downstream_gene_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152184

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

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

Jun 09, 2022

The c.929C>T (p.P310L) alteration is located in exon 10 (coding exon 9) of the CCDC83 gene. This alteration results from a C to T substitution at nucleotide position 929, causing the proline (P) at amino acid position 310 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

0.089

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.0030

.;T

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.044

LIST_S2

Benign

0.69

T;T

M_CAP

Benign

0.016

MetaRNN

Benign

0.090

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.28

PROVEAN

Uncertain

-3.1

D;D

REVEL

Benign

0.093

Sift

Benign

0.039

D;T

Sift4G

Benign

0.24

T;T

Polyphen

0.047

B;B

Vest4

0.18

MutPred

0.33

.;Gain of stability (P = 0.0121);

MVP

0.32

MPC

0.029

ClinPred

0.86

GERP RS

1.0

Varity_R

0.065

gMVP

0.071

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