11-64342057-G-C

Variant names:

• chr11-64342057-G-C
• rs993261018
• NM_032251.6:c.739G>C

Variant summary

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

The NM_032251.6(CCDC88B):​c.739G>C​(p.Ala247Pro) 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. 15/22 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. A247T) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CCDC88B NM_032251.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.692
• Publications: 0 publications found

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]

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=0.109859765).

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.739G>C	p.Ala247Pro	missense	Exon 8 of 27	NP_115627.6
	MIR7155	NR_106977.1		n.-153C>G		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC88B	ENST00000356786.10	TSL:1 MANE Select	c.739G>C	p.Ala247Pro	missense	Exon 8 of 27	ENSP00000349238.5	A6NC98-1
	CCDC88B	ENST00000971518.1		c.739G>C	p.Ala247Pro	missense	Exon 8 of 26	ENSP00000641577.1
	CCDC88B	ENST00000463837.5	TSL:2	n.783G>C		non_coding_transcript_exon	Exon 8 of 25

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	10
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0032	T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
PhyloP100		-0.69
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.028
Sift	Uncertain	0.022	D
Sift4G	Uncertain	0.034	D
Polyphen		0.73	P
Vest4		0.14
MutPred		0.27		Gain of catalytic residue at A247 (P = 0.001)
MVP		0.16
MPC		0.87
ClinPred		0.28	T
GERP RS		0.65
Varity_R		0.23
gMVP		0.63
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs993261018; hg19: chr11-64109529;