Variant chr12-82353312-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014167.5(CCDC59):c.565G>A(p.Glu189Lys) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.0000546 in 1,592,028 control chromosomes in the GnomAD database, with no homozygous occurrence. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000058 ( 0 hom. )

Consequence

CCDC59
NM_014167.5 missense, splice_region

Scores

Splicing: ADA: 0.9997

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.94

Variant links:

Genes affected

CCDC59 (HGNC:25005): (coiled-coil domain containing 59) Enables RNA binding activity. Predicted to be located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

CCDC59 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC59	NM_014167.5 linkuse as main transcript	c.565G>A	p.Glu189Lys	missense_variant, splice_region_variant	4/4	ENST00000256151.8
CCDC59	NR_033192.1 linkuse as main transcript	n.538G>A		splice_region_variant, non_coding_transcript_exon_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
CCDC59	ENST00000256151.8 linkuse as main transcript	c.565G>A	p.Glu189Lys	missense_variant, splice_region_variant	4/4	1	NM_014167.5	P1
CCDC59	ENST00000552377.5 linkuse as main transcript	c.464+3648G>A		intron_variant		5
CCDC59	ENST00000548126.1 linkuse as main transcript	n.519G>A		splice_region_variant, non_coding_transcript_exon_variant	4/4	2
CCDC59	ENST00000550589.1 linkuse as main transcript	n.1628G>A		splice_region_variant, non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152030

Hom.:

Cov.:

show subpopulations

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000349

AC:

AN:

228990

Hom.:

AF XY:

0.0000323

AC XY:

AN XY:

123826

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:

0.0000655

Gnomad OTH exome

AF:

0.000182

GnomAD4 exome

AF:

0.0000583

AC:

AN:

1439998

Hom.:

Cov.:

AF XY:

0.0000600

AC XY:

AN XY:

716142

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000733

Gnomad4 OTH exome

AF:

0.0000505

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152030

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74250

show subpopulations

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:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000432

Hom.:

Bravo

AF:

0.0000113

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000412

AC:

EpiCase

AF:

0.0000551

EpiControl

AF:

0.0000597

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

Sep 26, 2022

The c.565G>A (p.E189K) alteration is located in exon 4 (coding exon 4) of the CCDC59 gene. This alteration results from a G to A substitution at nucleotide position 565, causing the glutamic acid (E) at amino acid position 189 to be replaced by a lysine (K). 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

0.46

BayesDel_addAF

Pathogenic

0.30

BayesDel_noAF

Pathogenic

0.38

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.23

Eigen

Pathogenic

0.89

Eigen_PC

Pathogenic

0.87

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.78

M_CAP

Benign

0.013

MetaRNN

Uncertain

0.47

MetaSVM

Uncertain

0.070

MutationAssessor

Pathogenic

3.0

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.64

PROVEAN

Uncertain

-2.6

REVEL

Uncertain

0.58

Sift

Uncertain

0.0060

Sift4G

Uncertain

0.0080

Polyphen

1.0

Vest4

0.49

MVP

0.34

MPC

0.26

ClinPred

0.76

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.56

gMVP

0.39

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.96

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

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