Variant 18-33211952-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001105528.4(CCDC178):c.2182G>A(p.Asp728Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000373 in 1,609,766 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: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

CCDC178
NM_001105528.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.547

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 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=0.044318825).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC178	NM_001105528.4 linkuse as main transcript	c.2182G>A	p.Asp728Asn	missense_variant	20/23	ENST00000383096.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC178	ENST00000383096.8 linkuse as main transcript	c.2182G>A	p.Asp728Asn	missense_variant	20/23	5	NM_001105528.4	A2	Q5BJE1-1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151898

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000402

AC:

AN:

248634

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134444

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000888

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000343

AC:

AN:

1457750

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725174

show subpopulations

Gnomad4 AFR exome

AF:

0.0000600

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:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152016

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74294

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

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

Oct 18, 2021

The c.2182G>A (p.D728N) alteration is located in exon 19 (coding exon 18) of the CCDC178 gene. This alteration results from a G to A substitution at nucleotide position 2182, causing the aspartic acid (D) at amino acid position 728 to be replaced by an asparagine (N). 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

0.11

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Benign

0.57

DEOGEN2

Benign

0.0036

T;.;T;.;.;.;.

Eigen

Benign

-0.98

Eigen_PC

Benign

-0.99

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.84

T;T;.;D;T;.;T

M_CAP

Benign

0.0058

MetaRNN

Benign

0.044

T;T;T;T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.69

N;.;N;.;.;.;N

MutationTaster

Benign

1.0

N;N;N;N;N;N;N;N

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.49

N;.;N;N;N;.;.

REVEL

Benign

0.0070

Sift

Benign

0.15

T;.;T;T;T;.;.

Sift4G

Uncertain

0.013

D;D;D;D;D;D;D

Polyphen

0.0070

B;.;B;B;B;B;.

Vest4

0.12

MutPred

0.25

Gain of MoRF binding (P = 0.0526);.;Gain of MoRF binding (P = 0.0526);.;Gain of MoRF binding (P = 0.0526);Gain of MoRF binding (P = 0.0526);Gain of MoRF binding (P = 0.0526);

MVP

0.092

MPC

0.018

ClinPred

0.089

GERP RS

1.1

Varity_R

0.030

gMVP

0.038

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

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