Variant 7-5925673-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PP3_Moderate

The ENST00000325974.9(CCZ1):c.1435T>A(p.Phe479Ile) variant causes a missense change involving the alteration of a conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 35)

Exomes 𝑓: 0.000065 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CCZ1
ENST00000325974.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.84

Variant links:

Genes affected

CCZ1 (HGNC:21691): (CCZ1 homolog, vacuolar protein trafficking and biogenesis associated) Enables guanyl-nucleotide exchange factor activity. Predicted to be involved in vesicle-mediated transport. Located in intracellular membrane-bounded organelle. Part of Mon1-Ccz1 complex. [provided by Alliance of Genome Resources, Apr 2022]

CCZ1 links:

RSPH10B (HGNC:27362): (radial spoke head 10 homolog B)

RSPH10B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.847

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCZ1	NM_015622.6 linkuse as main transcript	c.1435T>A	p.Phe479Ile	missense_variant	15/15	ENST00000325974.9	NP_056437.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCZ1	ENST00000325974.9 linkuse as main transcript	c.1435T>A	p.Phe479Ile	missense_variant	15/15	1	NM_015622.6	ENSP00000325681	P1

Frequencies

GnomAD3 genomes

AF:

0.0000529

AC:

AN:

151178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000243

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000667

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000738

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000938

AC:

AN:

245222

Hom.:

AF XY:

0.000113

AC XY:

AN XY:

132968

show subpopulations

Gnomad AFR exome

AF:

0.0000621

Gnomad AMR exome

AF:

0.000274

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000549

Gnomad SAS exome

AF:

0.0000662

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000812

Gnomad OTH exome

AF:

0.000169

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000653

AC:

AN:

1454706

Hom.:

Cov.:

AF XY:

0.0000801

AC XY:

AN XY:

723848

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000429

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.0000551

Gnomad4 OTH exome

AF:

0.000133

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000529

AC:

AN:

151298

Hom.:

Cov.:

AF XY:

0.0000947

AC XY:

AN XY:

73904

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.0000666

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000738

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000184

Hom.:

ExAC

AF:

0.000115

AC:

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

Apr 04, 2024

The c.1435T>A (p.F479I) alteration is located in exon 15 (coding exon 15) of the CCZ1 gene. This alteration results from a T to A substitution at nucleotide position 1435, causing the phenylalanine (F) at amino acid position 479 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

BayesDel_addAF

Pathogenic

0.25

BayesDel_noAF

Pathogenic

0.42

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.36

Eigen

Uncertain

0.63

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Pathogenic

0.99

M_CAP

Uncertain

0.089

MetaRNN

Pathogenic

0.85

MetaSVM

Uncertain

-0.12

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.84

PROVEAN

Uncertain

-3.1

REVEL

Pathogenic

0.68

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.0050

Vest4

0.95

MVP

0.63

ClinPred

0.55

GERP RS

4.8

Varity_R

0.50

gMVP

0.72

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