Variant 7-5900505-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_015622.6(CCZ1):c.251T>C(p.Leu84Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00103 in 1,601,020 control chromosomes in the GnomAD database, including 6 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00054 ( 1 hom., cov: 26)

Exomes 𝑓: 0.0011 ( 5 hom. )

Consequence

CCZ1
NM_015622.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.46

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 -4 ACMG points.

BS2

High Homozygotes in GnomAdExome4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCZ1	NM_015622.6 linkuse as main transcript	c.251T>C	p.Leu84Ser	missense_variant	3/15	ENST00000325974.9	NP_056437.4	P86790P86791
CCZ1	XM_047420465.1 linkuse as main transcript	c.251T>C	p.Leu84Ser	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.251T>C	p.Leu84Ser	missense_variant	3/15	1	NM_015622.6	ENSP00000325681.6	P86791
CCZ1	ENST00000628813.2 linkuse as main transcript	c.218+124T>C		intron_variant		2		ENSP00000486988.1	F8WD66
CCZ1	ENST00000461592.1 linkuse as main transcript	n.417T>C		non_coding_transcript_exon_variant	2/2	2
CCZ1	ENST00000478672.1 linkuse as main transcript	n.270T>C		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes

AF:

0.000537

AC:

AN:

149108

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000175

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000977

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00105

Gnomad OTH

AF:

0.000484

GnomAD3 exomes

AF:

0.000477

AC:

AN:

161314

Hom.:

AF XY:

0.000518

AC XY:

AN XY:

86846

show subpopulations

Gnomad AFR exome

AF:

0.0000845

Gnomad AMR exome

AF:

0.000113

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000123

Gnomad FIN exome

AF:

0.000121

Gnomad NFE exome

AF:

0.000873

Gnomad OTH exome

AF:

0.000734

GnomAD4 exome

AF:

0.00108

AC:

1565

AN:

1451912

Hom.:

Cov.:

AF XY:

0.00106

AC XY:

763

AN XY:

722148

show subpopulations

Gnomad4 AFR exome

AF:

0.000153

Gnomad4 AMR exome

AF:

0.000161

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000142

Gnomad4 FIN exome

AF:

0.000113

Gnomad4 NFE exome

AF:

0.00134

Gnomad4 OTH exome

AF:

0.000834

GnomAD4 genome

AF:

0.000537

AC:

AN:

149108

Hom.:

Cov.:

AF XY:

0.000482

AC XY:

AN XY:

72652

show subpopulations

Gnomad4 AFR

AF:

0.000175

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000977

Gnomad4 NFE

AF:

0.00105

Gnomad4 OTH

AF:

0.000484

Alfa

AF:

0.000696

Hom.:

Bravo

AF:

0.000570

ESP6500AA

AF:

0.000243

AC:

ESP6500EA

AF:

0.000961

AC:

ExAC

AF:

0.000304

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

Dec 20, 2023

The c.251T>C (p.L84S) alteration is located in exon 3 (coding exon 3) of the CCZ1 gene. This alteration results from a T to C substitution at nucleotide position 251, causing the leucine (L) at amino acid position 84 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

Uncertain

0.15

BayesDel_noAF

Pathogenic

0.38

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.25

Eigen

Uncertain

0.67

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Pathogenic

0.98

M_CAP

Uncertain

0.11

MetaRNN

Uncertain

0.63

MetaSVM

Uncertain

-0.23

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.95

PROVEAN

Uncertain

-4.2

REVEL

Uncertain

0.64

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0040

Vest4

0.97

MVP

0.21

ClinPred

0.28

GERP RS

4.7

Varity_R

0.75

gMVP

0.84

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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