11-64340679-C-T

Variant names:

• chr11-64340679-C-T
• NM_032251.6:c.133C>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032251.6(CCDC88B):​c.133C>T​(p.Pro45Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,136 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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. P45A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CCDC88B NM_032251.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.178

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]

LOC102723878 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03404239).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC88B	NM_032251.6	c.133C>T	p.Pro45Ser	missense_variant	Exon 2 of 27	ENST00000356786.10	NP_115627.6
LOC102723878	NR_188518.1	n.114G>A		non_coding_transcript_exon_variant	Exon 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC88B	ENST00000356786.10	c.133C>T	p.Pro45Ser	missense_variant	Exon 2 of 27	1	NM_032251.6	ENSP00000349238.5
CCDC88B	ENST00000463837.5	n.177C>T		non_coding_transcript_exon_variant	Exon 2 of 25	2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460136 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 726440

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	5.1
DANN	Benign	0.84
DEOGEN2	Benign	0.0011	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.034	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.0	N
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.27	N
REVEL	Benign	0.014
Sift	Benign	0.73	T
Sift4G	Benign	0.65	T
Polyphen		0.0040	B
Vest4		0.23
MutPred		0.24		Loss of catalytic residue at P45 (P = 0.0016);
MVP		0.055
MPC		0.26
ClinPred		0.031	T
GERP RS		-1.5
Varity_R		0.029
gMVP		0.16

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-64108151;