Variant 11-85895320-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001286159.2(CCDC83):c.539C>A(p.Thr180Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 18)

Exomes 𝑓: 0.000017 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CCDC83
NM_001286159.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.697

Variant links:

Genes affected

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

CCDC83 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0684537).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC83	NM_001286159.2 linkuse as main transcript	c.539C>A	p.Thr180Asn	missense_variant	6/11	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.539C>A	p.Thr180Asn	missense_variant	6/11	1	NM_001286159.2	ENSP00000344512	P1	Q8IWF9-1
CCDC83	ENST00000526729.1 linkuse as main transcript	c.257C>A	p.Thr86Asn	missense_variant	3/8	1		ENSP00000434373
CCDC83	ENST00000280245.8 linkuse as main transcript	c.539C>A	p.Thr180Asn	missense_variant	6/12	2		ENSP00000280245		Q8IWF9-2
CCDC83	ENST00000529676.2 linkuse as main transcript	n.114C>A		non_coding_transcript_exon_variant	2/5	5

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

73644

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000171

AC:

AN:

818442

Hom.:

Cov.:

AF XY:

0.0000142

AC XY:

AN XY:

421592

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000285

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000206

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

73692

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34574

Gnomad4 AFR

AF:

0.00

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

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

May 26, 2024

The c.539C>A (p.T180N) alteration is located in exon 6 (coding exon 5) of the CCDC83 gene. This alteration results from a C to A substitution at nucleotide position 539, causing the threonine (T) at amino acid position 180 to be replaced by an asparagine (N). 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

0.14

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Benign

0.79

DEOGEN2

Benign

0.0052

.;T

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.83

FATHMM_MKL

Benign

0.053

LIST_S2

Benign

0.37

T;T

M_CAP

Benign

0.0097

MetaRNN

Benign

0.068

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

L;L

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.3

N;N

REVEL

Benign

0.028

Sift

Benign

0.17

T;T

Sift4G

Uncertain

0.051

T;T

Polyphen

0.078

B;B

Vest4

0.36

MutPred

0.25

Gain of methylation at K182 (P = 0.1023);Gain of methylation at K182 (P = 0.1023);

MVP

0.030

MPC

0.028

ClinPred

0.053

GERP RS

2.7

Varity_R

0.065

gMVP

0.21

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over