18-33212012-T-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001105528.4(CCDC178):c.2122A>G(p.Thr708Ala) 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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCDC178 NM_001105528.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.688

Genes affected

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

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.014610767).
• BP6: Variant 18-33212012-T-C is Benign according to our data. Variant chr18-33212012-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2327770.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC178	NM_001105528.4	c.2122A>G	p.Thr708Ala	missense_variant	20/23	ENST00000383096.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC178	ENST00000383096.8	c.2122A>G	p.Thr708Ala	missense_variant	20/23	5	NM_001105528.4	A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 18, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.81
Cadd	Benign	0.0050
Dann	Benign	0.14
DEOGEN2	Benign	0.00059	T;.;T;.;.;.;.
Eigen	Benign	-2.3
Eigen_PC	Benign	-2.3
FATHMM_MKL	Benign	0.0012	N
LIST_S2	Benign	0.33	T;T;.;T;T;.;T
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.015	T;T;T;T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-0.49	N;.;N;.;.;.;N
MutationTaster	Benign	1.0	N;N;N;N;N;N;N;N
PrimateAI	Benign	0.38	T
PROVEAN	Benign	0.20	N;.;N;N;N;.;.
REVEL	Benign	0.010
Sift	Benign	1.0	T;.;T;T;T;.;.
Sift4G	Benign	0.93	T;T;T;T;T;T;T
Polyphen		0.0	B;.;B;B;B;B;.
Vest4		0.066
MutPred		0.20		Gain of helix (P = 0.0854);.;Gain of helix (P = 0.0854);.;Gain of helix (P = 0.0854);Gain of helix (P = 0.0854);Gain of helix (P = 0.0854);
MVP		0.095
MPC		0.017
ClinPred		0.035	T
GERP RS		-3.8
Varity_R		0.018
gMVP		0.015

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr18-30791976;