11-64341491-C-T

Variant names:

• chr11-64341491-C-T
• NM_032251.6:c.518C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032251.6(CCDC88B):​c.518C>T​(p.Ala173Val) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A173S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CCDC88B NM_032251.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.501

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.085537046).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC88B	NM_032251.6	c.518C>T	p.Ala173Val	missense_variant	Exon 6 of 27	ENST00000356786.10	NP_115627.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC88B	ENST00000356786.10	c.518C>T	p.Ala173Val	missense_variant	Exon 6 of 27	1	NM_032251.6	ENSP00000349238.5
CCDC88B	ENST00000463837.5	n.562C>T		non_coding_transcript_exon_variant	Exon 6 of 25	2
CCDC88B	ENST00000494080.5	n.-115C>T		upstream_gene_variant		2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 08, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.518C>T (p.A173V) alteration is located in exon 6 (coding exon 6) of the CCDC88B gene. This alteration results from a C to T substitution at nucleotide position 518, causing the alanine (A) at amino acid position 173 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	14
DANN	Benign	0.97
DEOGEN2	Benign	0.043	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.049	N
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.086	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	2.0	M
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.036
Sift	Benign	0.045	D
Sift4G	Uncertain	0.0090	D
Polyphen		0.058	B
Vest4		0.18
MutPred		0.31		Loss of disorder (P = 0.1197);
MVP		0.048
MPC		0.29
ClinPred		0.15	T
GERP RS		-0.12
Varity_R		0.10
gMVP		0.38

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr11-64108963;