Genetic Variant NM_015603.3:c.251C>T (chr19-47260628-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_015603.3(CCDC9):c.251C>T(p.Pro84Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000197 in 1,523,392 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

CCDC9
NM_015603.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.881

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: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.060385883).

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.251C>T	p.Pro84Leu	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.251C>T	p.Pro84Leu	missense	Exon 5 of 12	ENSP00000221922.5	Q9Y3X0
CCDC9	ENST00000643617.1		c.251C>T	p.Pro84Leu	missense	Exon 5 of 14	ENSP00000494410.1	A0A2R8Y4Z8
CCDC9	ENST00000851059.1		c.251C>T	p.Pro84Leu	missense	Exon 5 of 15	ENSP00000521127.1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152226

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000146

AC:

AN:

1371166

Hom.:

Cov.:

AF XY:

0.00000148

AC XY:

AN XY:

675274

show subpopulations

African (AFR)

AF:

0.0000328

AC:

AN:

30524

American (AMR)

AF:

0.00

AC:

AN:

30828

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20474

East Asian (EAS)

AF:

0.00

AC:

AN:

39108

South Asian (SAS)

AF:

0.00

AC:

AN:

72128

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40106

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4370

European-Non Finnish (NFE)

AF:

9.29e-7

AC:

AN:

1076990

Other (OTH)

AF:

0.00

AC:

AN:

56638

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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:

0.00000657

AC:

AN:

152226

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41452

American (AMR)

AF:

0.00

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10632

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

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

0.080

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.0060

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.69

M_CAP

Benign

0.017

MetaRNN

Benign

0.060

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.46

PhyloP100

0.88

PrimateAI

Benign

0.44

PROVEAN

Benign

-1.8

REVEL

Benign

0.057

Sift

Benign

0.14

Sift4G

Benign

0.40

Polyphen

0.13

Vest4

0.31

MutPred

0.14

Loss of glycosylation at P84 (P = 0.0213)

MVP

0.13

MPC

0.10

ClinPred

0.098

GERP RS

2.3

Varity_R

0.037

gMVP

0.42

Mutation Taster

=74/26

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

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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