Genetic Variant CCZ1:p.Ala4Val (chr7-5898810-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -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. 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

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015622.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCZ1	NM_015622.6	MANE Select	c.11C>T	p.Ala4Val	missense	Exon 1 of 15	NP_056437.4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCZ1	ENST00000325974.9	TSL:1 MANE Select	c.11C>T	p.Ala4Val	missense	Exon 1 of 15	ENSP00000325681.6	P86791
CCZ1	ENST00000928077.1		c.11C>T	p.Ala4Val	missense	Exon 1 of 15	ENSP00000598136.1
CCZ1	ENST00000928076.1		c.11C>T	p.Ala4Val	missense	Exon 1 of 15	ENSP00000598135.1

Frequencies

GnomAD3 genomes

AF:

0.0000932

AC:

AN:

118044

Hom.:

Cov.:

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

6564

American (AMR)

AF:

0.000136

AC:

AN:

7342

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

9106

East Asian (EAS)

AF:

0.00

AC:

AN:

20910

South Asian (SAS)

AF:

0.0000618

AC:

AN:

16182

European-Finnish (FIN)

AF:

0.0000436

AC:

AN:

22958

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1262

European-Non Finnish (NFE)

AF:

0.000132

AC:

AN:

173654

Other (OTH)

AF:

0.000176

AC:

AN:

17048

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

African (AFR)

AF:

0.000101

AC:

AN:

29740

American (AMR)

AF:

0.000240

AC:

AN:

12516

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2954

East Asian (EAS)

AF:

0.00

AC:

AN:

3116

South Asian (SAS)

AF:

0.00

AC:

AN:

3182

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7054

Middle Eastern (MID)

AF:

0.00

AC:

AN:

226

European-Non Finnish (NFE)

AF:

0.0000701

AC:

AN:

57072

Other (OTH)

AF:

0.000651

AC:

AN:

1536

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.44

BayesDel_addAF

Benign

-0.068

BayesDel_noAF

Benign

-0.33

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.013

Eigen

Benign

-0.57

Eigen_PC

Benign

-0.47

FATHMM_MKL

Benign

0.28

M_CAP

Uncertain

0.26

MetaRNN

Benign

0.18

MetaSVM

Benign

-1.1

PhyloP100

1.1

PrimateAI

Uncertain

0.79

PROVEAN

Benign

-0.39

REVEL

Benign

0.091

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Vest4

0.30

MutPred

0.41

Loss of helix (P = 0.0017)

MVP

0.068

ClinPred

0.94

GERP RS

1.9

PromoterAI

0.0091

Neutral

(source)

Varity_R

0.13

gMVP

0.48

Mutation Taster

=95/5

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over