Variant 7-5919854-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_015622.6(CCZ1):c.994G>A(p.Val332Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 1,580,512 control chromosomes in the GnomAD database, including 9,614 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.26 ( 896 hom., cov: 27)

Exomes 𝑓: 0.26 ( 8718 hom. )

Consequence

CCZ1
NM_015622.6 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.961

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 Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014893413).

BP6

Variant 7-5919854-G-A is Benign according to our data. Variant chr7-5919854-G-A is described in ClinVar as [Benign]. Clinvar id is 769704.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCZ1	NM_015622.6 linkuse as main transcript	c.994G>A	p.Val332Ile	missense_variant	12/15	ENST00000325974.9	NP_056437.4
CCZ1	XM_047420465.1 linkuse as main transcript	c.955-3533G>A		intron_variant			XP_047276421.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
CCZ1	ENST00000325974.9 linkuse as main transcript	c.994G>A	p.Val332Ile	missense_variant	12/15	1	NM_015622.6	ENSP00000325681	P1
CCZ1	ENST00000628813.2 linkuse as main transcript	c.*663G>A		3_prime_UTR_variant	11/14	2		ENSP00000486988
CCZ1	ENST00000474507.1 linkuse as main transcript	n.2129G>A		non_coding_transcript_exon_variant	1/4	2

Frequencies

GnomAD3 genomes

AF:

0.264

AC:

38677

AN:

146594

Hom.:

896

Cov.:

show subpopulations

Gnomad AFR

AF:

0.276

Gnomad AMI

AF:

0.241

Gnomad AMR

AF:

0.322

Gnomad ASJ

AF:

0.332

Gnomad EAS

AF:

0.219

Gnomad SAS

AF:

0.321

Gnomad FIN

AF:

0.236

Gnomad MID

AF:

0.286

Gnomad NFE

AF:

0.244

Gnomad OTH

AF:

0.265

GnomAD4 exome

AF:

0.256

AC:

366914

AN:

1433800

Hom.:

8718

Cov.:

AF XY:

0.257

AC XY:

183560

AN XY:

712988

show subpopulations

Gnomad4 AFR exome

AF:

0.272

Gnomad4 AMR exome

AF:

0.355

Gnomad4 ASJ exome

AF:

0.334

Gnomad4 EAS exome

AF:

0.234

Gnomad4 SAS exome

AF:

0.324

Gnomad4 FIN exome

AF:

0.236

Gnomad4 NFE exome

AF:

0.246

Gnomad4 OTH exome

AF:

0.261

GnomAD4 genome

AF:

0.264

AC:

38721

AN:

146712

Hom.:

896

Cov.:

AF XY:

0.264

AC XY:

18909

AN XY:

71494

show subpopulations

Gnomad4 AFR

AF:

0.276

Gnomad4 AMR

AF:

0.323

Gnomad4 ASJ

AF:

0.332

Gnomad4 EAS

AF:

0.219

Gnomad4 SAS

AF:

0.321

Gnomad4 FIN

AF:

0.236

Gnomad4 NFE

AF:

0.244

Gnomad4 OTH

AF:

0.266

Alfa

AF:

0.273

Hom.:

198

ExAC

AF:

0.283

AC:

34378

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jun 22, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.52

DANN

Benign

0.63

DEOGEN2

Benign

0.033

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.021

MetaRNN

Benign

0.0015

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.17

REVEL

Benign

0.025

Sift

Benign

0.44

Sift4G

Benign

0.54

Vest4

0.056

ClinPred

0.00088

GERP RS

-5.1

Varity_R

0.012

gMVP

0.094

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