Variant chr18-33223153-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001105528.4(CCDC178):c.1885T>A(p.Leu629Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,606,678 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

CCDC178
NM_001105528.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.388

Variant links:

Genes affected

CCDC178 (HGNC:29588): (coiled-coil domain containing 178) Located in ciliary basal body. [provided by Alliance of Genome Resources, Apr 2022]

CCDC178 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.0700894).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC178	NM_001105528.4 linkuse as main transcript	c.1885T>A	p.Leu629Ile	missense_variant	18/23	ENST00000383096.8	NP_001098998.1	Q5BJE1-1A1L4G8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC178	ENST00000383096.8 linkuse as main transcript	c.1885T>A	p.Leu629Ile	missense_variant	18/23	5	NM_001105528.4	ENSP00000372576.3		Q5BJE1-1

Frequencies

GnomAD3 genomes

AF:

0.0000396

AC:

AN:

151662

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000484

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000773

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000406

AC:

AN:

246444

Hom.:

AF XY:

0.0000299

AC XY:

AN XY:

133806

show subpopulations

Gnomad AFR exome

AF:

0.000131

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000394

Gnomad SAS exome

AF:

0.0000331

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000894

AC:

AN:

1454902

Hom.:

Cov.:

AF XY:

0.00000691

AC XY:

AN XY:

723818

show subpopulations

Gnomad4 AFR exome

AF:

0.0000302

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000279

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000461

AC:

AN:

151776

Hom.:

Cov.:

AF XY:

0.0000405

AC XY:

AN XY:

74116

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000968

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000162

Hom.:

ExAC

AF:

0.0000414

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 01, 2022

The c.1885T>A (p.L629I) alteration is located in exon 17 (coding exon 16) of the CCDC178 gene. This alteration results from a T to A substitution at nucleotide position 1885, causing the leucine (L) at amino acid position 629 to be replaced by an isoleucine (I). 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

0.18

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.85

DEOGEN2

Benign

0.026

T;.;T;.;.;.

Eigen

Benign

0.013

Eigen_PC

Benign

-0.13

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.76

T;T;.;T;.;T

M_CAP

Benign

0.019

MetaRNN

Benign

0.070

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

L;.;L;.;.;L

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.77

N;.;N;N;.;.

REVEL

Benign

0.12

Sift

Pathogenic

0.0

D;.;D;D;.;.

Sift4G

Benign

0.21

T;D;T;T;T;T

Polyphen

1.0

D;.;D;D;D;.

Vest4

0.41

MVP

0.061

MPC

0.14

ClinPred

0.21

GERP RS

3.7

Varity_R

0.19

gMVP

0.037

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over