11-64342057-G-A

Position:

• chr11-64342057-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.692

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]

CCDC88B (HGNC:):

ACMG classification

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/exons	MANE	Protein	UniProt
CCDC88B	NM_032251.6	c.739G>A	p.Ala247Thr	missense_variant	8/27	ENST00000356786.10	NP_115627.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC88B	ENST00000356786.10	c.739G>A	p.Ala247Thr	missense_variant	8/27	1	NM_032251.6	ENSP00000349238.5
CCDC88B	ENST00000463837.5	n.783G>A		non_coding_transcript_exon_variant	8/25	2
CCDC88B	ENST00000494080.5	n.201G>A		non_coding_transcript_exon_variant	2/20	2

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

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

May 30, 2024

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

Other links and lift over

dbSNP: rs993261018; hg19: chr11-64109529;