Variant 7-5912898-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015622.6(CCZ1):c.898A>C(p.Lys300Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000398 in 150,766 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000040 ( 0 hom., cov: 29)

Exomes 𝑓: 0.000019 ( 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: 6.86

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.25714326).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCZ1	NM_015622.6 linkuse as main transcript	c.898A>C	p.Lys300Gln	missense_variant	10/15	ENST00000325974.9	NP_056437.4
CCZ1	XM_047420465.1 linkuse as main transcript	c.898A>C	p.Lys300Gln	missense_variant	10/11		XP_047276421.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCZ1	ENST00000325974.9 linkuse as main transcript	c.898A>C	p.Lys300Gln	missense_variant	10/15	1	NM_015622.6	ENSP00000325681	P1
CCZ1	ENST00000628813.2 linkuse as main transcript	c.*567A>C		3_prime_UTR_variant	9/14	2		ENSP00000486988

Frequencies

GnomAD3 genomes

AF:

0.0000398

AC:

AN:

150766

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000658

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:

0.0000588

Gnomad OTH

AF:

0.000483

GnomAD3 exomes

AF:

0.0000296

AC:

AN:

236418

Hom.:

AF XY:

0.0000390

AC XY:

AN XY:

128066

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000312

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000106

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000280

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000193

AC:

AN:

1454536

Hom.:

Cov.:

AF XY:

0.0000249

AC XY:

AN XY:

723692

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000226

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000815

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000163

Gnomad4 OTH exome

AF:

0.0000333

GnomAD4 genome

AF:

0.0000398

AC:

AN:

150766

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

73548

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000658

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.000483

Bravo

AF:

0.0000264

ExAC

AF:

0.0000165

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

Oct 25, 2022

The c.898A>C (p.K300Q) alteration is located in exon 10 (coding exon 10) of the CCZ1 gene. This alteration results from a A to C substitution at nucleotide position 898, causing the lysine (K) at amino acid position 300 to be replaced by a glutamine (Q). 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

-0.14

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.045

Eigen

Benign

-0.13

Eigen_PC

Benign

0.057

FATHMM_MKL

Uncertain

0.96

M_CAP

Benign

0.0031

MetaRNN

Benign

0.26

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-1.2

REVEL

Benign

0.089

Sift

Benign

0.13

Sift4G

Benign

0.40

Vest4

0.46

MutPred

0.69

Loss of ubiquitination at K300 (P = 0.0174);

MVP

0.19

ClinPred

0.73

GERP RS

4.3

Varity_R

0.12

gMVP

0.66

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