Variant chr12-82353189-T-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.688A>G(p.Met230Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000454 in 1,608,874 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

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

Exomes 𝑓: 0.000048 ( 1 hom. )

Consequence

CCDC59
NM_014167.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.05

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=0.066452175).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC59	NM_014167.5 linkuse as main transcript	c.688A>G	p.Met230Val	missense_variant	4/4	ENST00000256151.8
CCDC59	NR_033192.1 linkuse as main transcript	n.661A>G		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.688A>G	p.Met230Val	missense_variant	4/4	1	NM_014167.5	P1
CCDC59	ENST00000552377.5 linkuse as main transcript	c.464+3771A>G		intron_variant		5
CCDC59	ENST00000548126.1 linkuse as main transcript	n.642A>G		non_coding_transcript_exon_variant	4/4	2
CCDC59	ENST00000550589.1 linkuse as main transcript	n.1751A>G		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152164

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:

0.000414

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000889

AC:

AN:

247358

Hom.:

AF XY:

0.000120

AC XY:

AN XY:

133604

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:

0.000683

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000178

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000481

AC:

AN:

1456592

Hom.:

Cov.:

AF XY:

0.0000649

AC XY:

AN XY:

724450

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:

0.000729

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.0000998

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152282

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74466

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:

0.000415

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.000157

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Nov 08, 2022

The c.688A>G (p.M230V) alteration is located in exon 4 (coding exon 4) of the CCDC59 gene. This alteration results from a A to G substitution at nucleotide position 688, causing the methionine (M) at amino acid position 230 to be replaced by a valine (V). 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

0.16

BayesDel_addAF

Benign

-0.021

BayesDel_noAF

Uncertain

0.10

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.055

Eigen

Uncertain

0.65

Eigen_PC

Pathogenic

0.66

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.76

M_CAP

Benign

0.0058

MetaRNN

Benign

0.066

MetaSVM

Benign

-0.31

MutationAssessor

Uncertain

2.2

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-2.2

REVEL

Benign

0.26

Sift

Benign

0.033

Sift4G

Benign

0.062

Polyphen

0.95

Vest4

0.26

MutPred

0.52

Loss of MoRF binding (P = 0.1009);

MVP

0.17

MPC

0.052

ClinPred

0.21

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.29

gMVP

0.37

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