19-47260379-G-T

Variant names:

• chr19-47260379-G-T
• rs1390076894
• NM_015603.3:c.167G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_015603.3(CCDC9):​c.167G>T​(p.Arg56Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000206 in 1,453,316 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R56Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: CCDC9 NM_015603.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.56
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.167G>T	p.Arg56Leu	missense	Exon 4 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.167G>T	p.Arg56Leu	missense	Exon 4 of 12	ENSP00000221922.5	Q9Y3X0
	CCDC9	ENST00000643617.1		c.167G>T	p.Arg56Leu	missense	Exon 4 of 14	ENSP00000494410.1	A0A2R8Y4Z8
	CCDC9	ENST00000851059.1		c.167G>T	p.Arg56Leu	missense	Exon 4 of 15	ENSP00000521127.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1453316 Hom.: 0 Cov.: 32 AF XY: 0.00000277 AC XY: 2 AN XY: 722330

African (AFR) AF: 0.00 AC: 0 AN: 33240

American (AMR) AF: 0.00 AC: 0 AN: 43464

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25902

East Asian (EAS) AF: 0.00 AC: 0 AN: 39254

South Asian (SAS) AF: 0.00 AC: 0 AN: 84812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52798

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00000271 AC: 3 AN: 1108032

Other (OTH) AF: 0.00 AC: 0 AN: 60056

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.59
BayesDel_addAF	Benign	-0.066	T
BayesDel_noAF	Benign	-0.33
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.92	D
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.40	T
MetaSVM	Benign	-0.74	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		4.6
PrimateAI	Uncertain	0.70	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.21
Sift	Uncertain	0.0040	D
Sift4G	Benign	0.13	T
Polyphen		1.0	D
Vest4		0.64
MutPred		0.17		Loss of MoRF binding (P = 0.0066)
MVP		0.40
MPC		0.57
ClinPred		0.96	D
GERP RS		3.4
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6
Varity_R		0.33
gMVP		0.58
Mutation Taster		=54/46	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: rs1390076894; hg19: chr19-47763636;