NM_015622.6:c.177T>G

Variant names:

• chr7-5900340-T-G
• rs1386289149
• NM_015622.6:c.177T>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_015622.6(CCZ1):​c.177T>G​(p.Ile59Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000702 in 1,424,098 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 28)
  • Exomes 𝑓: 0.0000070 (0 hom.)
• Consequence: CCZ1 NM_015622.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.44
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.177T>G	p.Ile59Met	missense	Exon 2 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.177T>G	p.Ile59Met	missense	Exon 2 of 15	ENSP00000325681.6	P86791
	CCZ1	ENST00000928077.1		c.177T>G	p.Ile59Met	missense	Exon 2 of 15	ENSP00000598136.1
	CCZ1	ENST00000928076.1		c.177T>G	p.Ile59Met	missense	Exon 2 of 15	ENSP00000598135.1

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD2 exomes AF: 0.00 AC: 0 AN: 212808 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000702 AC: 10 AN: 1424098 Hom.: 0 Cov.: 31 AF XY: 0.00000706 AC XY: 5 AN XY: 708182

African (AFR) AF: 0.00 AC: 0 AN: 32052

American (AMR) AF: 0.00 AC: 0 AN: 35112

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25136

East Asian (EAS) AF: 0.0000531 AC: 2 AN: 37692

South Asian (SAS) AF: 0.00 AC: 0 AN: 80500

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52148

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5628

European-Non Finnish (NFE) AF: 9.12e-7 AC: 1 AN: 1096758

Other (OTH) AF: 0.000118 AC: 7 AN: 59072

GnomAD4 genome Cov.: 28

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

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	0.33
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.0
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.043	T
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.11
FATHMM_MKL	Uncertain	0.87	D
M_CAP	Benign	0.038	D
MetaRNN	Uncertain	0.55	D
MetaSVM	Benign	-1.0	T
PhyloP100		1.4
PrimateAI	Pathogenic	0.92	D
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.20
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.0060	D
Vest4		0.78
MutPred		0.38		Loss of methylation at K58 (P = 0.0343)
MVP		0.30
ClinPred		0.99	D
GERP RS		2.0
Varity_R		0.37
gMVP		0.50
Mutation Taster		=244/56	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

dbSNP: rs1386289149; hg19: chr7-5939971;