NM_032251.6:c.739G>A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_032251.6(CCDC88B):​c.739G>A​(p.Ala247Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 31)

Consequence

CCDC88B
NM_032251.6 missense

Scores

2
17

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.692
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]
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.043075383).
BP6
Variant 11-64342057-G-A is Benign according to our data. Variant chr11-64342057-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3264386.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CCDC88BNM_032251.6 linkc.739G>A p.Ala247Thr missense_variant Exon 8 of 27 ENST00000356786.10 NP_115627.6 A6NC98-1B2RTU8
MIR7155NR_106977.1 linkn.-153C>T upstream_gene_variant
MIR7155unassigned_transcript_1890 n.-190C>T upstream_gene_variant
MIR7155unassigned_transcript_1891 n.-153C>T upstream_gene_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CCDC88BENST00000356786.10 linkc.739G>A p.Ala247Thr missense_variant Exon 8 of 27 1 NM_032251.6 ENSP00000349238.5 A6NC98-1
CCDC88BENST00000463837.5 linkn.783G>A non_coding_transcript_exon_variant Exon 8 of 25 2
CCDC88BENST00000494080.5 linkn.201G>A non_coding_transcript_exon_variant Exon 2 of 20 2
MIR7155ENST00000615925.1 linkn.-153C>T upstream_gene_variant 6

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Cov.:
34
GnomAD4 genome
Cov.:
31
Bravo
AF:
0.00000378

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
May 30, 2024
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.078
BayesDel_addAF
Benign
-0.33
T
BayesDel_noAF
Benign
-0.71
CADD
Benign
5.7
DANN
Uncertain
0.98
DEOGEN2
Benign
0.00093
T
Eigen
Benign
-1.0
Eigen_PC
Benign
-1.0
FATHMM_MKL
Benign
0.066
N
LIST_S2
Benign
0.64
T
M_CAP
Benign
0.0098
T
MetaRNN
Benign
0.043
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.49
N
PrimateAI
Uncertain
0.59
T
PROVEAN
Benign
-0.22
N
REVEL
Benign
0.013
Sift
Benign
0.18
T
Sift4G
Benign
0.23
T
Polyphen
0.0010
B
Vest4
0.082
MutPred
0.086
Gain of phosphorylation at A247 (P = 0.0261);
MVP
0.067
MPC
0.26
ClinPred
0.046
T
GERP RS
0.65
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.060
gMVP
0.50

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs993261018; hg19: chr11-64109529; API