chr18-68837209-C-T

Position:

• chr18-68837209-C-T

Variant summary

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

The NM_024781.3(CCDC102B):​c.446C>T​(p.Ala149Val) 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. 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.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCDC102B NM_024781.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.368

Genes affected

CCDC102B (HGNC:26295): (coiled-coil domain containing 102B)

CCDC102B (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=0.047793806).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC102B	NM_024781.3	c.446C>T	p.Ala149Val	missense_variant	2/8	ENST00000360242.9	NP_079057.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC102B	ENST00000360242.9	c.446C>T	p.Ala149Val	missense_variant	2/8	1	NM_024781.3	ENSP00000353377.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 66

GnomAD4 genome Cov.: 32

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

Oct 19, 2024

The c.446C>T (p.A149V) alteration is located in exon 4 (coding exon 1) of the CCDC102B gene. This alteration results from a C to T substitution at nucleotide position 446, causing the alanine (A) at amino acid position 149 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	0.071
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	8.9
DANN	Benign	0.92
DEOGEN2	Benign	0.0017	.;T;.
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.048	N
LIST_S2	Benign	0.57	T;T;T
M_CAP	Benign	0.0090	T
MetaRNN	Benign	0.048	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	.;L;L
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-0.93	.;N;.
REVEL	Benign	0.041
Sift	Benign	0.36	.;T;.
Sift4G	Benign	0.32	T;T;T
Polyphen		0.037	.;B;.
Vest4		0.037
MutPred		0.069		Gain of methylation at K153 (P = 0.0888);Gain of methylation at K153 (P = 0.0888);Gain of methylation at K153 (P = 0.0888);
MVP		0.38
MPC		0.013
ClinPred		0.085	T
GERP RS		2.9
Varity_R		0.057
gMVP		0.057

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: chr18-66504446;