7-5900915-C-G

Variant names:

• chr7-5900915-C-G
• NM_015622.6:c.373C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_015622.6(CCZ1):​c.373C>G​(p.Gln125Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: CCZ1 NM_015622.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.50
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2978384).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015622.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCZ1	NM_015622.6	MANE Select	c.373C>G	p.Gln125Glu	missense	Exon 4 of 15	NP_056437.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCZ1	ENST00000325974.9	TSL:1 MANE Select	c.373C>G	p.Gln125Glu	missense	Exon 4 of 15	ENSP00000325681.6	P86791
	CCZ1	ENST00000928077.1		c.373C>G	p.Gln125Glu	missense	Exon 4 of 15	ENSP00000598136.1
	CCZ1	ENST00000928076.1		c.373C>G	p.Gln125Glu	missense	Exon 4 of 15	ENSP00000598135.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 19

GnomAD4 genome Cov.: 23

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.075	D
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.017	T
Eigen	Benign	0.19
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Pathogenic	0.99	D
M_CAP	Benign	0.0077	T
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.93	T
PhyloP100		7.5
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.55	N
REVEL	Benign	0.26
Sift	Benign	0.22	T
Sift4G	Benign	0.58	T
Vest4		0.54
MutPred		0.41		Gain of disorder (P = 0.0472)
MVP		0.15
ClinPred		0.98	D
GERP RS		4.8
Varity_R		0.26
gMVP		0.51
Mutation Taster		=250/50	polymorphism

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

Other links and lift over

hg19: chr7-5940546;