19-47260810-G-C

Variant names:

• chr19-47260810-G-C
• rs201974732
• NM_015603.3:c.433G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015603.3(CCDC9):​c.433G>C​(p.Asp145His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,998 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. 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. D145G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CCDC9 NM_015603.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.33
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20364514).

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.433G>C	p.Asp145His	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.433G>C	p.Asp145His	missense	Exon 5 of 12	ENSP00000221922.5	Q9Y3X0
	CCDC9	ENST00000643617.1		c.433G>C	p.Asp145His	missense	Exon 5 of 14	ENSP00000494410.1	A0A2R8Y4Z8
	CCDC9	ENST00000851059.1		c.433G>C	p.Asp145His	missense	Exon 5 of 15	ENSP00000521127.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460998 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 726868

African (AFR) AF: 0.00 AC: 0 AN: 33434

American (AMR) AF: 0.00 AC: 0 AN: 44510

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26076

East Asian (EAS) AF: 0.00 AC: 0 AN: 39654

South Asian (SAS) AF: 0.00 AC: 0 AN: 86212

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53360

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111644

Other (OTH) AF: 0.00 AC: 0 AN: 60348

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Uncertain	24
DANN	Benign	0.96
DEOGEN2	Benign	0.0065	T
Eigen	Uncertain	0.33
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.76	N
PhyloP100		3.3
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.13
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.057	T
Polyphen		1.0	D
Vest4		0.56
MutPred		0.15		Gain of MoRF binding (P = 0.1323)
MVP		0.43
MPC		0.49
ClinPred		0.54	D
GERP RS		3.3
Varity_R		0.069
gMVP		0.22
Mutation Taster		=79/21	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: rs201974732; hg19: chr19-47764067;