7-5898861-C-A

Variant names:

• chr7-5898861-C-A
• rs1445954869
• NM_015622.6:c.62C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_015622.6(CCZ1):​c.62C>A​(p.Pro21Gln) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P21L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000087 (0 hom., cov: 13)
  • Failed GnomAD Quality Control
• Consequence: CCZ1 NM_015622.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.21
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.18199804).

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.62C>A	p.Pro21Gln	missense	Exon 1 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.62C>A	p.Pro21Gln	missense	Exon 1 of 15	ENSP00000325681.6	P86791
	CCZ1	ENST00000928077.1		c.62C>A	p.Pro21Gln	missense	Exon 1 of 15	ENSP00000598136.1
	CCZ1	ENST00000928076.1		c.62C>A	p.Pro21Gln	missense	Exon 1 of 15	ENSP00000598135.1

Frequencies

GnomAD3 genomes AF: 0.00000867 AC: 1 AN: 115334 Hom.: 0 Cov.: 13

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000843

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 5

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000867 AC: 1 AN: 115334 Hom.: 0 Cov.: 13 AF XY: 0.0000184 AC XY: 1 AN XY: 54364

African (AFR) AF: 0.00 AC: 0 AN: 29204

American (AMR) AF: 0.0000843 AC: 1 AN: 11858

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2910

East Asian (EAS) AF: 0.00 AC: 0 AN: 3260

South Asian (SAS) AF: 0.00 AC: 0 AN: 3110

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7032

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 268

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 55510

Other (OTH) AF: 0.00 AC: 0 AN: 1488

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.052	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.18	T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.13
FATHMM_MKL	Uncertain	0.85	D
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.0	T
PhyloP100		4.2
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	0.050	N
REVEL	Benign	0.033
Sift	Uncertain	0.020	D
Sift4G	Benign	0.063	T
Vest4		0.30
MutPred		0.34		Loss of glycosylation at P21 (P = 0.0206)
MVP		0.068
ClinPred		0.99	D
GERP RS		3.0
PromoterAI		0.076	Neutral
Varity_R		0.12
gMVP		0.40
Mutation Taster		=83/17	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: rs1445954869; hg19: chr7-5938492;