NM_015603.3:c.251C>G

Variant names:

• chr19-47260628-C-G
• rs1049188328
• NM_015603.3:c.251C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015603.3(CCDC9):​c.251C>G​(p.Pro84Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000729 in 1,371,166 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P84L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: CCDC9 NM_015603.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.881
• Publications: 0 publications found

Genes affected

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

ENSG00000298666 (HGNC:):

ACMG classification

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=0.05968523).

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>G	p.Pro84Arg	missense	Exon 5 of 12	NP_056418.1	Q9Y3X0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC9	ENST00000221922.11	TSL:1 MANE Select	c.251C>G	p.Pro84Arg	missense	Exon 5 of 12	ENSP00000221922.5	Q9Y3X0
	CCDC9	ENST00000643617.1		c.251C>G	p.Pro84Arg	missense	Exon 5 of 14	ENSP00000494410.1	A0A2R8Y4Z8
	CCDC9	ENST00000851059.1		c.251C>G	p.Pro84Arg	missense	Exon 5 of 15	ENSP00000521127.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.29e-7 AC: 1 AN: 1371166 Hom.: 0 Cov.: 32 AF XY: 0.00000148 AC XY: 1 AN XY: 675274

African (AFR) AF: 0.00 AC: 0 AN: 30524

American (AMR) AF: 0.00 AC: 0 AN: 30828

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20474

East Asian (EAS) AF: 0.0000256 AC: 1 AN: 39108

South Asian (SAS) AF: 0.00 AC: 0 AN: 72128

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40106

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4370

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1076990

Other (OTH) AF: 0.00 AC: 0 AN: 56638

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	16
DANN	Benign	0.63
DEOGEN2	Benign	0.048	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.060	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.88
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.61	N
REVEL	Benign	0.056
Sift	Benign	0.065	T
Sift4G	Benign	0.34	T
Polyphen		0.34	B
Vest4		0.38
MutPred		0.18		Gain of MoRF binding (P = 0.009)
MVP		0.13
MPC		0.24
ClinPred		0.074	T
GERP RS		2.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.045
gMVP		0.44
Mutation Taster		=71/29	polymorphism

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

Other links and lift over

dbSNP: rs1049188328; hg19: chr19-47763885;