chr7-5905104-C-T

Variant names:

• chr7-5905104-C-T
• rs772144601
• NM_015622.6:c.533C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_015622.6(CCZ1):​c.533C>T​(p.Thr178Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000719 in 1,598,910 control chromosomes in the GnomAD database, including 4 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000048 (0 hom., cov: 27)
  • Exomes 𝑓: 0.000074 (4 hom.)
• Consequence: CCZ1 NM_015622.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.82
• Publications: 3 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High Homozygotes in GnomAdExome4 at 4 gene

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.533C>T	p.Thr178Met	missense	Exon 7 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.533C>T	p.Thr178Met	missense	Exon 7 of 15	ENSP00000325681.6	P86791
	CCZ1	ENST00000928077.1		c.533C>T	p.Thr178Met	missense	Exon 7 of 15	ENSP00000598136.1
	CCZ1	ENST00000928076.1		c.533C>T	p.Thr178Met	missense	Exon 7 of 15	ENSP00000598135.1

Frequencies

GnomAD3 genomes AF: 0.0000477 AC: 7 AN: 146830 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.0000258

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000669

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000222

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000592

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000847 AC: 21 AN: 247818 AF XY: 0.000104

Gnomad AFR exome AF: 0.000127

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000178

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000744 AC: 108 AN: 1452080 Hom.: 4 Cov.: 32 AF XY: 0.0000983 AC XY: 71 AN XY: 722078

African (AFR) AF: 0.00 AC: 0 AN: 32418

American (AMR) AF: 0.0000225 AC: 1 AN: 44540

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26006

East Asian (EAS) AF: 0.000110 AC: 4 AN: 36310

South Asian (SAS) AF: 0.000571 AC: 48 AN: 84132

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52566

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5744

European-Non Finnish (NFE) AF: 0.0000441 AC: 49 AN: 1110352

Other (OTH) AF: 0.0000833 AC: 5 AN: 60012

GnomAD4 genome AF: 0.0000477 AC: 7 AN: 146830 Hom.: 0 Cov.: 27 AF XY: 0.0000700 AC XY: 5 AN XY: 71438

African (AFR) AF: 0.0000258 AC: 1 AN: 38690

American (AMR) AF: 0.0000669 AC: 1 AN: 14940

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3432

East Asian (EAS) AF: 0.000222 AC: 1 AN: 4508

South Asian (SAS) AF: 0.00 AC: 0 AN: 4410

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9974

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.0000592 AC: 4 AN: 67620

Other (OTH) AF: 0.00 AC: 0 AN: 2034

Alfa AF: 0.000198 Hom.: 1

ExAC AF: 0.000108 AC: 13

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	Uncertain	0.12	D
BayesDel_noAF	Pathogenic	0.24
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Pathogenic	0.98	D
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.62	D
MetaSVM	Benign	-0.79	T
PhyloP100		7.8
PrimateAI	Uncertain	0.75	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.21
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.0020	D
Vest4		0.84
MVP		0.31
ClinPred		0.34	T
GERP RS		5.8
Varity_R		0.24
gMVP		0.54
Mutation Taster		=90/10	polymorphism

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

Other links and lift over

dbSNP: rs772144601; hg19: chr7-5944735; COSMIC: COSV100382768; COSMIC: COSV100382768;