Genetic Variant NM_032251.6:c.659G>A (chr11-64341726-G-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_032251.6(CCDC88B):c.659G>A(p.Arg220His) variant causes a missense change. The variant allele was found at a frequency of 0.000000703 in 1,422,748 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

CCDC88B
NM_032251.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.40

Publications

0 publications found

Variant links:

Genes affected

CCDC88B (HGNC:26757): (coiled-coil domain containing 88B) This gene encodes a member of the hook-related protein family. Members of this family are characterized by an N-terminal potential microtubule binding domain, a central coiled-coiled and a C-terminal Hook-related domain. The encoded protein may be involved in linking organelles to microtubules. [provided by RefSeq, Oct 2009]

CCDC88B links:

MIR7155 (HGNC:50005): (microRNA 7155) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

MIR7155 links:

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ACMG classification

Classification was made for transcript

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_032251.6. 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
	CCDC88B	NM_032251.6	MANE Select	c.659G>A	p.Arg220His	missense	Exon 7 of 27	NP_115627.6
	MIR7155	NR_106977.1		n.*123C>T		downstream_gene	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCDC88B	ENST00000356786.10	TSL:1 MANE Select	c.659G>A	p.Arg220His	missense	Exon 7 of 27	ENSP00000349238.5	A6NC98-1
CCDC88B	ENST00000971518.1		c.659G>A	p.Arg220His	missense	Exon 7 of 26	ENSP00000641577.1
CCDC88B	ENST00000463837.5	TSL:2	n.703G>A		non_coding_transcript_exon	Exon 7 of 25

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.03e-7

AC:

AN:

1422748

Hom.:

Cov.:

AF XY:

0.00000142

AC XY:

AN XY:

705610

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31882

American (AMR)

AF:

0.00

AC:

AN:

36364

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23264

East Asian (EAS)

AF:

0.00

AC:

AN:

39496

South Asian (SAS)

AF:

0.00

AC:

AN:

80042

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51346

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5562

European-Non Finnish (NFE)

AF:

9.12e-7

AC:

AN:

1096116

Other (OTH)

AF:

0.00

AC:

AN:

58676

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

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

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

Uncertain

0.37

BayesDel_addAF

Uncertain

0.042

BayesDel_noAF

Benign

-0.18

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.24

Eigen

Uncertain

0.61

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.83

M_CAP

Uncertain

0.14

MetaRNN

Uncertain

0.62

MetaSVM

Uncertain

-0.18

MutationAssessor

Uncertain

2.8

PhyloP100

4.4

PrimateAI

Uncertain

0.75

PROVEAN

Uncertain

-3.5

REVEL

Uncertain

0.32

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.028

Polyphen

1.0

Vest4

0.61

MutPred

0.32

Loss of MoRF binding (P = 0.0477)

MVP

0.48

MPC

1.0

ClinPred

0.98

GERP RS

4.0

Varity_R

0.29

gMVP

0.95

Mutation Taster

=85/15

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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