chr18-68837145-G-C

Variant names:

• chr18-68837145-G-C
• rs544688546
• NM_024781.3:c.382G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_024781.3(CCDC102B):​c.382G>C​(p.Glu128Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000242 in 1,613,932 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000021 (0 hom.)
• Consequence: CCDC102B NM_024781.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.60
• Publications: 1 publications found

Genes affected

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3181165).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC102B	NM_024781.3	c.382G>C	p.Glu128Gln	missense_variant	Exon 2 of 8	ENST00000360242.9	NP_079057.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC102B	ENST00000360242.9	c.382G>C	p.Glu128Gln	missense_variant	Exon 2 of 8	1	NM_024781.3	ENSP00000353377.5

Frequencies

GnomAD3 genomes AF: 0.0000526 AC: 8 AN: 152152 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000241 AC: 6 AN: 248862 AF XY: 0.00000741

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000532

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000212 AC: 31 AN: 1461780 Hom.: 0 Cov.: 66 AF XY: 0.0000206 AC XY: 15 AN XY: 727188

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000252 AC: 28 AN: 1111930

Other (OTH) AF: 0.0000497 AC: 3 AN: 60396

GnomAD4 genome AF: 0.0000526 AC: 8 AN: 152152 Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4 AN XY: 74322

African (AFR) AF: 0.0000483 AC: 2 AN: 41420

American (AMR) AF: 0.00 AC: 0 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.0000675 Hom.: 0

Bravo AF: 0.0000453

ExAC AF: 0.0000165 AC: 2

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 12, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.382G>C (p.E128Q) alteration is located in exon 4 (coding exon 1) of the CCDC102B gene. This alteration results from a G to C substitution at nucleotide position 382, causing the glutamic acid (E) at amino acid position 128 to be replaced by a glutamine (Q). 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	Uncertain	0.36
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.41
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.090	.;T;.;.
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.95	D;D;D;D
M_CAP	Benign	0.0098	T
MetaRNN	Benign	0.32	T;T;T;T
MetaSVM	Benign	-0.75	T
MutationAssessor	Uncertain	2.3	.;M;.;M
PhyloP100		8.6
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-2.5	.;N;.;.
REVEL	Benign	0.088
Sift	Uncertain	0.011	.;D;.;.
Sift4G	Uncertain	0.026	D;D;D;D
Polyphen		0.99	.;D;.;.
Vest4		0.26, 0.22
MutPred		0.16		Loss of ubiquitination at K126 (P = 0.0326);Loss of ubiquitination at K126 (P = 0.0326);Loss of ubiquitination at K126 (P = 0.0326);Loss of ubiquitination at K126 (P = 0.0326);
MVP		0.92
MPC		0.093
ClinPred		0.71	D
GERP RS		5.4
PromoterAI		0.018	Neutral
Varity_R		0.23
gMVP		0.11
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs544688546; hg19: chr18-66504382;