Variant chr12-82358332-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_014167.5(CCDC59):c.45T>G(p.Ile15Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000496 in 1,613,970 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

CCDC59
NM_014167.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -6.25

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.01686117).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC59	NM_014167.5 linkuse as main transcript	c.45T>G	p.Ile15Met	missense_variant	1/4	ENST00000256151.8
CCDC59	NR_033192.1 linkuse as main transcript	n.127+347T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC59	ENST00000256151.8 linkuse as main transcript	c.45T>G	p.Ile15Met	missense_variant	1/4	1	NM_014167.5	P1

Frequencies

GnomAD3 genomes

AF:

0.000315

AC:

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00111

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.000479

GnomAD3 exomes

AF:

0.0000558

AC:

AN:

250938

Hom.:

AF XY:

0.0000515

AC XY:

AN XY:

135816

show subpopulations

Gnomad AFR exome

AF:

0.000804

Gnomad AMR exome

AF:

0.0000289

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:

0.0000219

AC:

AN:

1461774

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

727200

show subpopulations

Gnomad4 AFR exome

AF:

0.000747

Gnomad4 AMR exome

AF:

0.0000224

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:

0.0000993

GnomAD4 genome

AF:

0.000315

AC:

AN:

152196

Hom.:

Cov.:

AF XY:

0.000323

AC XY:

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.00111

Gnomad4 AMR

AF:

0.0000654

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:

0.000479

Alfa

AF:

0.000290

Hom.:

Bravo

AF:

0.000295

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000824

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

Apr 04, 2023

The c.45T>G (p.I15M) alteration is located in exon 1 (coding exon 1) of the CCDC59 gene. This alteration results from a T to G substitution at nucleotide position 45, causing the isoleucine (I) at amino acid position 15 to be replaced by a methionine (M). 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

0.066

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.0010

DANN

Benign

0.83

DEOGEN2

Benign

0.0046

.;T

Eigen

Benign

-1.8

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.00014

LIST_S2

Benign

0.28

T;T

M_CAP

Benign

0.0020

MetaRNN

Benign

0.017

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

.;N

MutationTaster

Benign

1.0

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.070

N;N

REVEL

Benign

0.018

Sift

Benign

0.095

T;T

Sift4G

Benign

0.13

T;T

Polyphen

0.0040

.;B

Vest4

0.12

MVP

0.014

MPC

0.032

ClinPred

0.057

GERP RS

-10

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.7

Varity_R

0.047

gMVP

0.076

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

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