7-5898861-C-T

Variant names:

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

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>T​(p.Pro21Leu) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 13)
  • Exomes 𝑓: 0.0000027 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CCZ1 NM_015622.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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=0.1734392).

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>T	p.Pro21Leu	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>T	p.Pro21Leu	missense	Exon 1 of 15	ENSP00000325681.6	P86791
	CCZ1	ENST00000928077.1		c.62C>T	p.Pro21Leu	missense	Exon 1 of 15	ENSP00000598136.1
	CCZ1	ENST00000928076.1		c.62C>T	p.Pro21Leu	missense	Exon 1 of 15	ENSP00000598135.1

Frequencies

GnomAD3 genomes Cov.: 13

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000271 AC: 1 AN: 369274 Hom.: 0 Cov.: 5 AF XY: 0.00000521 AC XY: 1 AN XY: 192070

African (AFR) AF: 0.00 AC: 0 AN: 7680

American (AMR) AF: 0.00 AC: 0 AN: 8194

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10700

East Asian (EAS) AF: 0.00 AC: 0 AN: 22724

South Asian (SAS) AF: 0.00 AC: 0 AN: 27452

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26298

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1572

European-Non Finnish (NFE) AF: 0.00000410 AC: 1 AN: 243636

Other (OTH) AF: 0.00 AC: 0 AN: 21018

GnomAD4 genome Cov.: 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	0.076
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.10	T
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.23
FATHMM_MKL	Uncertain	0.86	D
M_CAP	Uncertain	0.096	D
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.1	T
PhyloP100		4.2
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-0.80	N
REVEL	Benign	0.097
Sift	Uncertain	0.014	D
Sift4G	Benign	0.13	T
Vest4		0.33
MutPred		0.37		Loss of glycosylation at P21 (P = 0.0206)
MVP		0.043
ClinPred		0.99	D
GERP RS		3.0
PromoterAI		0.17	Neutral
Varity_R		0.11
gMVP		0.35
Mutation Taster		=89/11	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;