Genetic Variant CCDC9B:p.His2Leu (chr15-40340815-T-A) – 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_207380.3(CCDC9B):c.5A>T(p.His2Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,457,738 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

CCDC9B
NM_207380.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.11

Publications

0 publications found

Variant links:

Genes affected

CCDC9B (HGNC:33488): (coiled-coil domain containing 9B) Enables RNA binding activity. [provided by Alliance of Genome Resources, Apr 2022]

CCDC9B 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=0.22725737).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC9B	NM_207380.3 link	c.5A>T	p.His2Leu	missense_variant	Exon 1 of 11	ENST00000397536.7	NP_997263.3	Q6ZUT6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CCDC9B	ENST00000397536.7 link	c.5A>T	p.His2Leu	missense_variant	Exon 1 of 11	1	NM_207380.3	ENSP00000380670.3	Q6ZUT6
CCDC9B	ENST00000557973.1 link	n.106A>T		non_coding_transcript_exon_variant	Exon 1 of 3	3
CCDC9B	ENST00000558912.1 link	n.-177A>T		upstream_gene_variant		5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

238002

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.00000274

AC:

AN:

1457738

Hom.:

Cov.:

AF XY:

0.00000414

AC XY:

AN XY:

724854

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33392

American (AMR)

AF:

0.00

AC:

AN:

44330

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25966

East Asian (EAS)

AF:

0.00

AC:

AN:

39626

South Asian (SAS)

AF:

0.0000117

AC:

AN:

85386

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52358

Middle Eastern (MID)

AF:

0.000350

AC:

AN:

5720

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110698

Other (OTH)

AF:

0.0000166

AC:

AN:

60262

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.438

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

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 16, 2021

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.137A>T (p.H46L) alteration is located in exon 1 (coding exon 1) of the C15orf52 gene. This alteration results from a A to T substitution at nucleotide position 137, causing the histidine (H) at amino acid position 46 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.021

BayesDel_noAF

Benign

-0.27

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.026

Eigen

Benign

-0.091

Eigen_PC

Benign

-0.060

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.42

M_CAP

Benign

0.0028

MetaRNN

Benign

0.23

MetaSVM

Benign

-1.1

PhyloP100

2.1

PROVEAN

Benign

-2.3

Sift

Uncertain

0.0060

Sift4G

Uncertain

0.028

Polyphen

0.78

Vest4

0.42

MutPred

0.35

Loss of catalytic residue at H46 (P = 0.0171);

MVP

0.27

MPC

0.16

ClinPred

0.88

GERP RS

2.6

PromoterAI

0.064

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.28

gMVP

0.31

Mutation Taster

=92/8

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over