Variant 7-77256501-G-A 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_020879.3(CCDC146):c.676G>A(p.Val226Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000475 in 1,600,730 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000043 ( 0 hom. )

Consequence

CCDC146
NM_020879.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0820

Variant links:

Genes affected

CCDC146 (HGNC:29296): (coiled-coil domain containing 146) Located in centriole. [provided by Alliance of Genome Resources, Apr 2022]

CCDC146 links:

(HGNC:):

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=0.034058154).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC146	NM_020879.3 linkuse as main transcript	c.676G>A	p.Val226Ile	missense_variant	6/19	ENST00000285871.5
LOC102723791	XR_927688.3 linkuse as main transcript	n.434+700C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC146	ENST00000285871.5 linkuse as main transcript	c.676G>A	p.Val226Ile	missense_variant	6/19	1	NM_020879.3	P1	Q8IYE0-1
	ENST00000476561.2 linkuse as main transcript	n.272+700C>T		intron_variant, non_coding_transcript_variant		4
CCDC146	ENST00000461882.1 linkuse as main transcript	n.312G>A		non_coding_transcript_exon_variant	3/4	3

Frequencies

GnomAD3 genomes

AF:

0.0000920

AC:

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000501

AC:

AN:

239432

Hom.:

AF XY:

0.0000540

AC XY:

AN XY:

129558

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000102

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000256

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000361

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000428

AC:

AN:

1448516

Hom.:

Cov.:

AF XY:

0.0000458

AC XY:

AN XY:

720476

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000247

Gnomad4 ASJ exome

AF:

0.0000387

Gnomad4 EAS exome

AF:

0.0000506

Gnomad4 SAS exome

AF:

0.000157

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000379

Gnomad4 OTH exome

AF:

0.0000501

GnomAD4 genome

AF:

0.0000920

AC:

AN:

152214

Hom.:

Cov.:

AF XY:

0.0000941

AC XY:

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000192

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000579

Hom.:

Bravo

AF:

0.0000453

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000577

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

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

Dec 13, 2021

The c.676G>A (p.V226I) alteration is located in exon 6 (coding exon 5) of the CCDC146 gene. This alteration results from a G to A substitution at nucleotide position 676, causing the valine (V) at amino acid position 226 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

0.068

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.54

Cadd

Benign

0.83

Dann

Benign

0.78

DEOGEN2

Benign

0.00075

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0047

LIST_S2

Benign

0.46

M_CAP

Benign

0.027

MetaRNN

Benign

0.034

MetaSVM

Benign

-0.77

MutationAssessor

Benign

1.7

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.32

REVEL

Benign

0.17

Sift

Benign

0.20

Sift4G

Benign

0.19

Polyphen

0.0040

Vest4

0.051

MVP

0.13

MPC

0.13

ClinPred

0.026

GERP RS

1.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.020

gMVP

0.036

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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