Variant 15-74244015-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_025055.5(CCDC33):c.52G>A(p.Ala18Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0015 in 1,612,508 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0015 ( 5 hom. )

Consequence

CCDC33
NM_025055.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.393

Variant links:

Genes affected

CCDC33 (HGNC:26552): (coiled-coil domain containing 33) Predicted to be active in peroxisome. [provided by Alliance of Genome Resources, Apr 2022]

CCDC33 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004213482).

BP6

Variant 15-74244015-G-A is Benign according to our data. Variant chr15-74244015-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3037179.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC33	NM_025055.5 linkuse as main transcript	c.52G>A	p.Ala18Thr	missense_variant	2/19	ENST00000398814.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC33	ENST00000398814.8 linkuse as main transcript	c.52G>A	p.Ala18Thr	missense_variant	2/19	2	NM_025055.5	P2	Q8N5R6-6
CCDC33	ENST00000635913.2 linkuse as main transcript	c.706G>A	p.Ala236Thr	missense_variant	3/20	5		A2

Frequencies

GnomAD3 genomes

AF:

0.00107

AC:

161

AN:

150992

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000974

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000919

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00158

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.00184

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00155

AC:

386

AN:

249016

Hom.:

AF XY:

0.00147

AC XY:

198

AN XY:

135128

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00223

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000223

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00233

Gnomad NFE exome

AF:

0.00204

Gnomad OTH exome

AF:

0.00381

GnomAD4 exome

AF:

0.00154

AC:

2257

AN:

1461442

Hom.:

Cov.:

AF XY:

0.00158

AC XY:

1150

AN XY:

727038

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.00219

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00259

Gnomad4 NFE exome

AF:

0.00173

Gnomad4 OTH exome

AF:

0.00142

GnomAD4 genome

AF:

0.00107

AC:

161

AN:

151066

Hom.:

Cov.:

AF XY:

0.000936

AC XY:

AN XY:

73680

show subpopulations

Gnomad4 AFR

AF:

0.0000972

Gnomad4 AMR

AF:

0.000918

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00158

Gnomad4 NFE

AF:

0.00184

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00170

Hom.:

Bravo

AF:

0.00105

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00207

AC:

ExAC

AF:

0.00179

AC:

217

EpiCase

AF:

0.00115

EpiControl

AF:

0.00142

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

CCDC33-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 29, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.91

Cadd

Benign

0.013

Dann

Benign

0.26

DEOGEN2

Benign

0.0019

T;.

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0021

LIST_S2

Benign

0.26

T;T

M_CAP

Benign

0.0030

MetaRNN

Benign

0.0042

T;T

MetaSVM

Benign

-0.96

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.24

Polyphen

0.0020

.;B

Vest4

0.043

MVP

0.085

MPC

0.078

ClinPred

0.018

GERP RS

-6.2

gMVP

0.12

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