Variant 15-74217353-C-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 ENST00000635913.2(CCDC33):c.82C>A(p.Leu28Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00219 in 1,290,132 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 6/9 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0021 ( 1 hom., cov: 31)

Exomes 𝑓: 0.0022 ( 8 hom. )

Consequence

CCDC33
ENST00000635913.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.44

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=0.006496072).

BP6

Variant 15-74217353-C-A is Benign according to our data. Variant chr15-74217353-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 2645537.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons
CCDC33	XM_011522085.4 linkuse as main transcript	c.82C>A	p.Leu28Met	missense_variant	1/21
CCDC33	XM_017022623.2 linkuse as main transcript	c.82C>A	p.Leu28Met	missense_variant	1/21
CCDC33	XM_017022624.2 linkuse as main transcript	c.82C>A	p.Leu28Met	missense_variant	1/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	Appris
CCDC33	ENST00000635913.2 linkuse as main transcript	c.82C>A	p.Leu28Met	missense_variant	1/20	5	A2
CCDC33	ENST00000559243.1 linkuse as main transcript	n.153C>A		non_coding_transcript_exon_variant	1/2	4
CCDC33	ENST00000560148.5 linkuse as main transcript	n.674-1144C>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00210

AC:

319

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000627

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00131

Gnomad ASJ

AF:

0.00461

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00310

Gnomad FIN

AF:

0.00113

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00323

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00259

AC:

357

AN:

137962

Hom.:

AF XY:

0.00250

AC XY:

187

AN XY:

74816

show subpopulations

Gnomad AFR exome

AF:

0.000152

Gnomad AMR exome

AF:

0.00196

Gnomad ASJ exome

AF:

0.00662

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00156

Gnomad FIN exome

AF:

0.000426

Gnomad NFE exome

AF:

0.00366

Gnomad OTH exome

AF:

0.00376

GnomAD4 exome

AF:

0.00220

AC:

2501

AN:

1137784

Hom.:

Cov.:

AF XY:

0.00216

AC XY:

1203

AN XY:

558184

show subpopulations

Gnomad4 AFR exome

AF:

0.000328

Gnomad4 AMR exome

AF:

0.00212

Gnomad4 ASJ exome

AF:

0.00471

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00180

Gnomad4 FIN exome

AF:

0.00136

Gnomad4 NFE exome

AF:

0.00225

Gnomad4 OTH exome

AF:

0.00243

GnomAD4 genome

AF:

0.00210

AC:

320

AN:

152348

Hom.:

Cov.:

AF XY:

0.00209

AC XY:

156

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.000625

Gnomad4 AMR

AF:

0.00131

Gnomad4 ASJ

AF:

0.00461

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00310

Gnomad4 FIN

AF:

0.00113

Gnomad4 NFE

AF:

0.00325

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00348

Hom.:

Bravo

AF:

0.00206

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00285

AC:

ExAC

AF:

0.00170

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2023

STRA6: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Uncertain

-0.040

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.045

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.29

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.54

M_CAP

Benign

0.0093

MetaRNN

Benign

0.0065

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.98

GERP RS

1.8

Splicing

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