7-5912947-T-C

Position:

• chr7-5912947-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_015622.6(CCZ1):​c.947T>C​(p.Val316Ala) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 29)
• Consequence: CCZ1 NM_015622.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.38

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

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.769

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCZ1	NM_015622.6	c.947T>C	p.Val316Ala	missense_variant	10/15	ENST00000325974.9	NP_056437.4
CCZ1	XM_047420465.1	c.947T>C	p.Val316Ala	missense_variant	10/11		XP_047276421.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCZ1	ENST00000325974.9	c.947T>C	p.Val316Ala	missense_variant	10/15	1	NM_015622.6	ENSP00000325681.6
CCZ1	ENST00000628813.2	c.*616T>C		3_prime_UTR_variant	9/14	2		ENSP00000486988.1

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 29

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 06, 2022

The c.947T>C (p.V316A) alteration is located in exon 10 (coding exon 10) of the CCZ1 gene. This alteration results from a T to C substitution at nucleotide position 947, causing the valine (V) at amino acid position 316 to be replaced by an alanine (A). 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	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.14
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.22	T
Eigen	Pathogenic	0.70
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Pathogenic	0.97	D
M_CAP	Benign	0.0038	T
MetaRNN	Pathogenic	0.77	D
MetaSVM	Benign	-0.37	T
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.90	D
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.26
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.017	D
Vest4		0.91
MutPred		0.67		Loss of sheet (P = 0.0315);
MVP		0.19
ClinPred		0.98	D
GERP RS		5.5
Varity_R		0.40
gMVP		0.70

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-5952578;