NM_032251.6:c.392A>C

Variant names:

• chr11-64341273-A-C
• NM_032251.6:c.392A>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.392A>C​(p.Glu131Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,860 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: CCDC88B NM_032251.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.00100
• 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]

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=0.1303457).

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.392A>C	p.Glu131Ala	missense	Exon 5 of 27	NP_115627.6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC88B	ENST00000356786.10	TSL:1 MANE Select	c.392A>C	p.Glu131Ala	missense	Exon 5 of 27	ENSP00000349238.5	A6NC98-1
	CCDC88B	ENST00000971518.1		c.392A>C	p.Glu131Ala	missense	Exon 5 of 26	ENSP00000641577.1
	CCDC88B	ENST00000463837.5	TSL:2	n.436A>C		non_coding_transcript_exon	Exon 5 of 25

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461860 Hom.: 0 Cov.: 36 AF XY: 0.00000413 AC XY: 3 AN XY: 727230

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53394

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1112006

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0057	T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0094	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.40	N
PhyloP100		0.0010
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.064
Sift	Benign	0.13	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.79	P
Vest4		0.41
MutPred		0.32		Loss of disorder (P = 0.04)
MVP		0.10
MPC		0.34
ClinPred		0.31	T
GERP RS		2.8
Varity_R		0.16
gMVP		0.42
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		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

hg19: chr11-64108745;