Genetic Variant CCDC9:p.Arg128Cys (chr19-47260759-C-T) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 4P and 1B. PM1PM2BP4

The NM_015603.3(CCDC9):c.382C>T(p.Arg128Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,608,976 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

CCDC9
NM_015603.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.911

Publications

0 publications found

Variant links:

Genes affected

CCDC9 (HGNC:24560): (coiled-coil domain containing 9) Enables RNA binding activity. [provided by Alliance of Genome Resources, Apr 2022]

CCDC9 links:

ENSG00000298666 (HGNC:):

ENSG00000298666 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM1

In a modified_residue Omega-N-methylarginine (size 0) in uniprot entity CCDC9_HUMAN

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.33403212).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015603.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC9	NM_015603.3	MANE Select	c.382C>T	p.Arg128Cys	missense	Exon 5 of 12	NP_056418.1	Q9Y3X0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCDC9	ENST00000221922.11	TSL:1 MANE Select	c.382C>T	p.Arg128Cys	missense	Exon 5 of 12	ENSP00000221922.5	Q9Y3X0
CCDC9	ENST00000643617.1		c.382C>T	p.Arg128Cys	missense	Exon 5 of 14	ENSP00000494410.1	A0A2R8Y4Z8
CCDC9	ENST00000851059.1		c.382C>T	p.Arg128Cys	missense	Exon 5 of 15	ENSP00000521127.1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000126

AC:

AN:

238980

AF XY:

0.00000764

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000302

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000573

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000935

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000158

AC:

AN:

1456826

Hom.:

Cov.:

AF XY:

0.0000166

AC XY:

AN XY:

724928

show subpopulations

African (AFR)

AF:

0.0000301

AC:

AN:

33174

American (AMR)

AF:

0.0000461

AC:

AN:

43352

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25804

East Asian (EAS)

AF:

0.0000506

AC:

AN:

39564

South Asian (SAS)

AF:

0.0000233

AC:

AN:

85846

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53094

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5724

European-Non Finnish (NFE)

AF:

0.0000144

AC:

AN:

1110124

Other (OTH)

AF:

0.00

AC:

AN:

60144

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152150

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74318

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41442

American (AMR)

AF:

0.00

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68012

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000850

Hom.:

Bravo

AF:

0.0000189

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.049

Eigen

Uncertain

0.34

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Benign

0.51

LIST_S2

Benign

0.75

M_CAP

Benign

0.055

MetaRNN

Benign

0.30

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.5

PhyloP100

0.91

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-2.3

REVEL

Benign

0.17

Sift

Benign

0.10

Sift4G

Uncertain

0.0020

Polyphen

1.0

Vest4

0.63

MutPred

0.35

Loss of methylation at R128 (P = 0.0011)

MVP

0.50

MPC

0.57

ClinPred

0.65

GERP RS

3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.11

gMVP

0.57

Mutation Taster

=79/21

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over