Variant 7-5900535-A-G 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.281A>G(p.Asn94Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000668 in 149,656 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000067 ( 0 hom., cov: 26)

Exomes 𝑓: 0.00011 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

CCZ1
NM_015622.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.31

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:

CCZ1 (HGNC:):

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=0.14238808).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCZ1	NM_015622.6 linkuse as main transcript	c.281A>G	p.Asn94Ser	missense_variant	3/15	ENST00000325974.9	NP_056437.4	P86790P86791
CCZ1	XM_047420465.1 linkuse as main transcript	c.281A>G	p.Asn94Ser	missense_variant	3/11		XP_047276421.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CCZ1	ENST00000325974.9 linkuse as main transcript	c.281A>G	p.Asn94Ser	missense_variant	3/15	1	NM_015622.6	ENSP00000325681.6	P86791
CCZ1	ENST00000628813.2 linkuse as main transcript	c.218+154A>G		intron_variant		2		ENSP00000486988.1	F8WD66
CCZ1	ENST00000461592.1 linkuse as main transcript	n.447A>G		non_coding_transcript_exon_variant	2/2	2
CCZ1	ENST00000478672.1 linkuse as main transcript	n.300A>G		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes

AF:

0.0000668

AC:

AN:

149656

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000125

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000665

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:

0.0000589

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000338

AC:

AN:

177648

Hom.:

AF XY:

0.0000415

AC XY:

AN XY:

96470

show subpopulations

Gnomad AFR exome

AF:

0.0000826

Gnomad AMR exome

AF:

0.00

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:

0.0000357

Gnomad OTH exome

AF:

0.000439

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000107

AC:

155

AN:

1452658

Hom.:

Cov.:

AF XY:

0.0000983

AC XY:

AN XY:

722448

show subpopulations

Gnomad4 AFR exome

AF:

0.000305

Gnomad4 AMR exome

AF:

0.0000909

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000262

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000116

Gnomad4 OTH exome

AF:

0.000150

GnomAD4 genome

AF:

0.0000668

AC:

AN:

149656

Hom.:

Cov.:

AF XY:

0.0000822

AC XY:

AN XY:

72976

show subpopulations

Gnomad4 AFR

AF:

0.000125

Gnomad4 AMR

AF:

0.0000665

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000589

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000198

Hom.:

ExAC

AF:

0.0000508

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

Sep 01, 2021

The c.281A>G (p.N94S) alteration is located in exon 3 (coding exon 3) of the CCZ1 gene. This alteration results from a A to G substitution at nucleotide position 281, causing the asparagine (N) at amino acid position 94 to be replaced by a serine (S). 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

-0.24

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.012

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.045

FATHMM_MKL

Uncertain

0.93

M_CAP

Benign

0.0051

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

D;N

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.35

REVEL

Benign

0.064

Sift

Benign

0.32

Sift4G

Benign

0.33

Vest4

0.27

MutPred

0.44

Gain of disorder (P = 0.1212);

MVP

0.043

ClinPred

0.23

GERP RS

4.7

Varity_R

0.060

gMVP

0.30

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