chr11-64341696-T-G

Position:

• chr11-64341696-T-G

Variant summary

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

The NM_032251.6(CCDC88B):​c.629T>G​(p.Met210Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000344 in 1,453,624 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: CCDC88B NM_032251.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.279

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=0.11561903).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC88B	NM_032251.6	c.629T>G	p.Met210Arg	missense_variant	7/27	ENST00000356786.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC88B	ENST00000356786.10	c.629T>G	p.Met210Arg	missense_variant	7/27	1	NM_032251.6	P1
CCDC88B	ENST00000463837.5	n.673T>G		non_coding_transcript_exon_variant	7/25	2
CCDC88B	ENST00000494080.5	n.91T>G		non_coding_transcript_exon_variant	1/20	2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000344 AC: 5 AN: 1453624 Hom.: 0 Cov.: 35 AF XY: 0.00000415 AC XY: 3 AN XY: 722918

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: 0.00000451

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 04, 2023

The c.629T>G (p.M210R) alteration is located in exon 7 (coding exon 7) of the CCDC88B gene. This alteration results from a T to G substitution at nucleotide position 629, causing the methionine (M) at amino acid position 210 to be replaced by an arginine (R). 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	0.15
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	16
DANN	Benign	0.97
DEOGEN2	Benign	0.015	T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.41	N
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.041
Sift	Uncertain	0.028	D
Sift4G	Benign	0.30	T
Polyphen		0.058	B
Vest4		0.52
MutPred		0.29		Gain of methylation at M210 (P = 0.0143);
MVP		0.18
MPC		0.65
ClinPred		0.19	T
GERP RS		-1.1
Varity_R		0.32
gMVP		0.88

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

LitVar

Other links and lift over

dbSNP: rs1036019748; hg19: chr11-64109168;