Genetic Variant CCDC9:p.Pro96Leu (chr19-47260664-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015603.3(CCDC9):c.287C>T(p.Pro96Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000217 in 1,381,986 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000022 ( 0 hom. )

Consequence

CCDC9
NM_015603.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0510

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.099547).

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.287C>T	p.Pro96Leu	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.287C>T	p.Pro96Leu	missense	Exon 5 of 12	ENSP00000221922.5	Q9Y3X0
CCDC9	ENST00000643617.1		c.287C>T	p.Pro96Leu	missense	Exon 5 of 14	ENSP00000494410.1	A0A2R8Y4Z8
CCDC9	ENST00000851059.1		c.287C>T	p.Pro96Leu	missense	Exon 5 of 15	ENSP00000521127.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000581

AC:

AN:

172016

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000439

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

0.00000217

AC:

AN:

1381986

Hom.:

Cov.:

AF XY:

0.00000147

AC XY:

AN XY:

681928

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

30834

American (AMR)

AF:

0.0000631

AC:

AN:

31680

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20806

East Asian (EAS)

AF:

0.00

AC:

AN:

39196

South Asian (SAS)

AF:

0.00

AC:

AN:

73266

European-Finnish (FIN)

AF:

0.00

AC:

AN:

43350

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4806

European-Non Finnish (NFE)

AF:

9.25e-7

AC:

AN:

1081072

Other (OTH)

AF:

0.00

AC:

AN:

56976

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0338994), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.392

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

Cov.:

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

0.064

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0065

Eigen

Benign

-0.85

Eigen_PC

Benign

-0.90

FATHMM_MKL

Benign

0.026

LIST_S2

Benign

0.71

M_CAP

Benign

0.0097

MetaRNN

Benign

0.10

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

PhyloP100

-0.051

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.96

REVEL

Benign

0.0040

Sift

Uncertain

0.015

Sift4G

Benign

0.18

Polyphen

0.0

Vest4

0.22

MutPred

0.20

Loss of glycosylation at P96 (P = 0.0242)

MVP

0.23

MPC

0.14

ClinPred

0.059

GERP RS

0.98

Varity_R

0.027

gMVP

0.45

Mutation Taster

=95/5

polymorphism

(source)

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

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over