Variant 7-5911886-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015622.6(CCZ1):c.806G>A(p.Arg269Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000139 in 1,436,894 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 28)

Exomes 𝑓: 0.000014 ( 1 hom. )

Consequence

CCZ1
NM_015622.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.76

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCZ1	NM_015622.6 linkuse as main transcript	c.806G>A	p.Arg269Lys	missense_variant	9/15	ENST00000325974.9	NP_056437.4	P86790P86791
CCZ1	XM_047420465.1 linkuse as main transcript	c.806G>A	p.Arg269Lys	missense_variant	9/11		XP_047276421.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCZ1	ENST00000325974.9 linkuse as main transcript	c.806G>A	p.Arg269Lys	missense_variant	9/15	1	NM_015622.6	ENSP00000325681.6		P86791
CCZ1	ENST00000628813.2 linkuse as main transcript	c.*475G>A		3_prime_UTR_variant	8/14	2		ENSP00000486988.1		F8WD66

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000862

AC:

AN:

231908

Hom.:

AF XY:

0.00000790

AC XY:

AN XY:

126542

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000682

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000139

AC:

AN:

1436894

Hom.:

Cov.:

AF XY:

0.0000196

AC XY:

AN XY:

714842

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000483

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000467

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000936

Hom.:

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

Aug 21, 2023

The c.806G>A (p.R269K) alteration is located in exon 9 (coding exon 9) of the CCZ1 gene. This alteration results from a G to A substitution at nucleotide position 806, causing the arginine (R) at amino acid position 269 to be replaced by a lysine (K). 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

Uncertain

0.043

BayesDel_noAF

Uncertain

0.010

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.0097

Eigen

Benign

-0.16

Eigen_PC

Benign

0.032

FATHMM_MKL

Pathogenic

0.98

M_CAP

Benign

0.0039

MetaRNN

Uncertain

0.43

MetaSVM

Benign

-0.94

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-0.37

REVEL

Benign

0.16

Sift

Benign

0.40

Sift4G

Benign

0.93

Vest4

0.60

MutPred

0.57

Gain of ubiquitination at R269 (P = 0.006);

MVP

0.42

ClinPred

0.94

GERP RS

4.5

Varity_R

0.20

gMVP

0.49

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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