Variant 11-85911324-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_001286159.2(CCDC83):c.716T>C(p.Ile239Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000845 in 1,611,448 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00041 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00089 ( 5 hom. )

Consequence

CCDC83
NM_001286159.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.02

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 Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.32477266).

BS2

High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC83	NM_001286159.2 linkuse as main transcript	c.716T>C	p.Ile239Thr	missense_variant	8/11	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.716T>C	p.Ile239Thr	missense_variant	8/11	1	NM_001286159.2	ENSP00000344512.3	Q8IWF9-1
CCDC83	ENST00000526729.1 linkuse as main transcript	c.431T>C	p.Ile144Thr	missense_variant	5/8	1		ENSP00000434373.1	H0YDV3
CCDC83	ENST00000280245.8 linkuse as main transcript	c.716T>C	p.Ile239Thr	missense_variant	8/12	2		ENSP00000280245.4	Q8IWF9-2
CCDC83	ENST00000529676.2 linkuse as main transcript	n.291T>C		non_coding_transcript_exon_variant	4/5	5

Frequencies

GnomAD3 genomes

AF:

0.000407

AC:

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

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:

0.000779

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000268

AC:

AN:

249692

Hom.:

AF XY:

0.000311

AC XY:

AN XY:

134892

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:

0.000574

Gnomad OTH exome

AF:

0.000330

GnomAD4 exome

AF:

0.000890

AC:

1299

AN:

1459168

Hom.:

Cov.:

AF XY:

0.000889

AC XY:

645

AN XY:

725854

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00108

Gnomad4 OTH exome

AF:

0.00153

GnomAD4 genome

AF:

0.000407

AC:

AN:

152280

Hom.:

Cov.:

AF XY:

0.000282

AC XY:

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.000217

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:

0.000779

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000745

Hom.:

Bravo

AF:

0.000465

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.000222

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

Jun 11, 2021

The c.716T>C (p.I239T) alteration is located in exon 8 (coding exon 7) of the CCDC83 gene. This alteration results from a T to C substitution at nucleotide position 716, causing the isoleucine (I) at amino acid position 239 to be replaced by a threonine (T). 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

Uncertain

0.43

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.032

.;T

Eigen

Benign

0.035

Eigen_PC

Benign

-0.0060

FATHMM_MKL

Benign

0.43

LIST_S2

Benign

0.70

T;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.32

T;T

MetaSVM

Benign

-0.90

MutationAssessor

Uncertain

2.3

M;M

PrimateAI

Uncertain

0.68

PROVEAN

Uncertain

-2.8

D;D

REVEL

Benign

0.22

Sift

Benign

0.13

T;T

Sift4G

Benign

0.28

T;T

Polyphen

0.61

P;P

Vest4

0.65

MVP

0.31

MPC

0.081

ClinPred

0.17

GERP RS

4.2

Varity_R

0.089

gMVP

0.13

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