Variant 7-5898810-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_015622.6(CCZ1):c.11C>T(p.Ala4Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 10/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000093 ( 0 hom., cov: 14)

Exomes 𝑓: 0.00011 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CCZ1
NM_015622.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.15

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.17918915).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCZ1	NM_015622.6 linkuse as main transcript	c.11C>T	p.Ala4Val	missense_variant	1/15	ENST00000325974.9	NP_056437.4
CCZ1	XM_047420465.1 linkuse as main transcript	c.11C>T	p.Ala4Val	missense_variant	1/11		XP_047276421.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
CCZ1	ENST00000325974.9 linkuse as main transcript	c.11C>T	p.Ala4Val	missense_variant	1/15	1	NM_015622.6	ENSP00000325681	P1
CCZ1	ENST00000628813.2 linkuse as main transcript	c.11C>T	p.Ala4Val	missense_variant	1/14	2		ENSP00000486988
CCZ1	ENST00000461592.1 linkuse as main transcript	n.86C>T		non_coding_transcript_exon_variant	1/2	2
CCZ1	ENST00000478672.1 linkuse as main transcript	n.30C>T		non_coding_transcript_exon_variant	1/3	2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

118044

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000101

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000240

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000701

Gnomad OTH

AF:

0.000659

GnomAD4 exome

AF:

0.000105

AC:

AN:

275026

Hom.:

Cov.:

AF XY:

0.000105

AC XY:

AN XY:

143538

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000136

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000618

Gnomad4 FIN exome

AF:

0.0000436

Gnomad4 NFE exome

AF:

0.000132

Gnomad4 OTH exome

AF:

0.000176

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000931

AC:

AN:

118136

Hom.:

Cov.:

AF XY:

0.0000891

AC XY:

AN XY:

56126

show subpopulations

Gnomad4 AFR

AF:

0.000101

Gnomad4 AMR

AF:

0.000240

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000701

Gnomad4 OTH

AF:

0.000651

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

Oct 12, 2022

The c.11C>T (p.A4V) alteration is located in exon 1 (coding exon 1) of the CCZ1 gene. This alteration results from a C to T substitution at nucleotide position 11, causing the alanine (A) at amino acid position 4 to be replaced by a valine (V). 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

Benign

-0.068

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.013

T;.

Eigen

Benign

-0.57

Eigen_PC

Benign

-0.47

FATHMM_MKL

Benign

0.28

M_CAP

Uncertain

0.26

MetaRNN

Benign

0.18

T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

D;N

PrimateAI

Uncertain

0.79

PROVEAN

Benign

-0.39

N;.

REVEL

Benign

0.091

Sift

Pathogenic

0.0

D;.

Sift4G

Pathogenic

0.0

D;D

Vest4

0.30

MutPred

0.41

Loss of helix (P = 0.0017);Loss of helix (P = 0.0017);

MVP

0.068

ClinPred

0.94

GERP RS

1.9

Varity_R

0.13

gMVP

0.48

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