Variant 11-85873238-G-C 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.123G>C(p.Glu41Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000449 in 1,559,734 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

CCDC83
NM_001286159.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.178

Variant links:

Genes affected

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

CCDC83 links:

CCDC83 (HGNC:):

CCDC83 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=0.17330539).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC83	NM_001286159.2 linkuse as main transcript	c.123G>C	p.Glu41Asp	missense_variant	3/11	ENST00000342404.8	NP_001273088.1	Q8IWF9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CCDC83	ENST00000342404.8 linkuse as main transcript	c.123G>C	p.Glu41Asp	missense_variant	3/11	1	NM_001286159.2	ENSP00000344512.3	Q8IWF9-1
CCDC83	ENST00000526729.1 linkuse as main transcript	c.6G>C	p.Glu2Asp	missense_variant	1/8	1		ENSP00000434373.1	H0YDV3
CCDC83	ENST00000280245.8 linkuse as main transcript	c.123G>C	p.Glu41Asp	missense_variant	3/12	2		ENSP00000280245.4	Q8IWF9-2
CCDC83	ENST00000529676.2 linkuse as main transcript	n.29G>C		non_coding_transcript_exon_variant	1/5	5

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

151998

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000967

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

GnomAD3 exomes

AF:

0.00000893

AC:

AN:

223922

Hom.:

AF XY:

0.00000823

AC XY:

AN XY:

121574

show subpopulations

Gnomad AFR exome

AF:

0.000136

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000213

AC:

AN:

1407736

Hom.:

Cov.:

AF XY:

0.00000285

AC XY:

AN XY:

700702

show subpopulations

Gnomad4 AFR exome

AF:

0.0000960

Gnomad4 AMR exome

AF:

0.00

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000263

AC:

AN:

151998

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74248

show subpopulations

Gnomad4 AFR

AF:

0.0000967

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:

0.0000264

ExAC

AF:

0.0000165

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

Oct 05, 2023

The c.123G>C (p.E41D) alteration is located in exon 3 (coding exon 2) of the CCDC83 gene. This alteration results from a G to C substitution at nucleotide position 123, causing the glutamic acid (E) at amino acid position 41 to be replaced by an aspartic acid (D). 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

0.32

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0039

.;T

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.25

FATHMM_MKL

Benign

0.094

LIST_S2

Benign

0.76

T;T

M_CAP

Benign

0.016

MetaRNN

Benign

0.17

T;T

MetaSVM

Benign

-0.83

MutationAssessor

Uncertain

2.2

M;M

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-1.5

N;N

REVEL

Benign

0.19

Sift

Benign

0.096

T;T

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;D

Vest4

0.15

MutPred

0.49

Loss of ubiquitination at K36 (P = 0.1191);Loss of ubiquitination at K36 (P = 0.1191);

MVP

0.29

MPC

0.18

ClinPred

0.41

GERP RS

1.9

Varity_R

0.072

gMVP

0.20

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