7-5919879-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_015622.6(CCZ1):​c.1019G>A​(p.Arg340Gln) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000060 ( 0 hom., cov: 26)
Exomes 𝑓: 0.000049 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

CCZ1
NM_015622.6 missense

Scores

3
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.99
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]

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=0.2538249).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CCZ1NM_015622.6 linkuse as main transcriptc.1019G>A p.Arg340Gln missense_variant 12/15 ENST00000325974.9 NP_056437.4
CCZ1XM_047420465.1 linkuse as main transcriptc.955-3508G>A intron_variant XP_047276421.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CCZ1ENST00000325974.9 linkuse as main transcriptc.1019G>A p.Arg340Gln missense_variant 12/151 NM_015622.6 ENSP00000325681 P1
CCZ1ENST00000628813.2 linkuse as main transcriptc.*688G>A 3_prime_UTR_variant 11/142 ENSP00000486988
CCZ1ENST00000474507.1 linkuse as main transcriptn.2154G>A non_coding_transcript_exon_variant 1/42

Frequencies

GnomAD3 genomes
AF:
0.0000602
AC:
9
AN:
149488
Hom.:
0
Cov.:
26
show subpopulations
Gnomad AFR
AF:
0.0000246
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:
0.0000972
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000104
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000454
AC:
11
AN:
242220
Hom.:
0
AF XY:
0.0000381
AC XY:
5
AN XY:
131178
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000123
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000111
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000946
Gnomad NFE exome
AF:
0.0000273
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0000494
AC:
72
AN:
1457394
Hom.:
0
Cov.:
35
AF XY:
0.0000565
AC XY:
41
AN XY:
725088
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000680
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000759
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.0000941
Gnomad4 NFE exome
AF:
0.0000523
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0000602
AC:
9
AN:
149488
Hom.:
0
Cov.:
26
AF XY:
0.0000686
AC XY:
5
AN XY:
72858
show subpopulations
Gnomad4 AFR
AF:
0.0000246
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000972
Gnomad4 NFE
AF:
0.000104
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000245
Hom.:
0
ExAC
AF:
0.0000494
AC:
6

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 submitterclinical testingAmbry GeneticsJan 30, 2024The c.1019G>A (p.R340Q) alteration is located in exon 12 (coding exon 12) of the CCZ1 gene. This alteration results from a G to A substitution at nucleotide position 1019, causing the arginine (R) at amino acid position 340 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
-0.19
T
BayesDel_noAF
Benign
-0.28
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.022
T
Eigen
Benign
-0.074
Eigen_PC
Benign
0.10
FATHMM_MKL
Uncertain
0.92
D
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.25
T
MetaSVM
Benign
-0.98
T
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.60
T
PROVEAN
Benign
-0.79
N
REVEL
Benign
0.19
Sift
Benign
0.14
T
Sift4G
Benign
0.35
T
Vest4
0.56
MutPred
0.51
Loss of helix (P = 0.1706);
MVP
0.19
ClinPred
0.10
T
GERP RS
5.0
Varity_R
0.15
gMVP
0.28

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs762538590; hg19: chr7-5959510; API