10-122836186-T-C

Variant names:

• chr10-122836186-T-C
• NM_022034.6:c.982A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_022034.6(CUZD1):​c.982A>G​(p.Ile328Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,448,434 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CUZD1 NM_022034.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0950
• Publications: 0 publications found

Genes affected

CUZD1 (HGNC:17937): (CUB and zona pellucida like domains 1) Predicted to be involved in trypsinogen activation. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

CUZD1 Gene-Disease associations (from GenCC):

• schizophrenia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ENSG00000286088 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12952742).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022034.6. 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
	CUZD1	NM_022034.6	MANE Select	c.982A>G	p.Ile328Val	missense	Exon 6 of 9	NP_071317.2
	CUZD1	NR_037912.2		n.845A>G		non_coding_transcript_exon	Exon 5 of 8
	FAM24B-CUZD1	NR_037915.1		n.1658A>G		non_coding_transcript_exon	Exon 8 of 11

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CUZD1	ENST00000392790.6	TSL:1 MANE Select	c.982A>G	p.Ile328Val	missense	Exon 6 of 9	ENSP00000376540.1	Q86UP6-1
	CUZD1	ENST00000368899.5	TSL:1	n.1095A>G		non_coding_transcript_exon	Exon 3 of 6
	CUZD1	ENST00000368900.5	TSL:1	n.*523A>G		non_coding_transcript_exon	Exon 5 of 8	ENSP00000357896.2	A0A0A0MRL2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1448434 Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1 AN XY: 720536

African (AFR) AF: 0.00 AC: 0 AN: 32366

American (AMR) AF: 0.00 AC: 0 AN: 40988

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25480

East Asian (EAS) AF: 0.00 AC: 0 AN: 39534

South Asian (SAS) AF: 0.00 AC: 0 AN: 83376

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53178

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5680

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1108110

Other (OTH) AF: 0.00 AC: 0 AN: 59722

GnomAD4 genome Cov.: 32

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	0.071
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	6.4
DANN	Benign	0.85
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.95	L
PhyloP100		0.095
PROVEAN	Benign	-0.34	N
REVEL	Benign	0.10
Sift	Benign	0.44	T
Sift4G	Benign	0.82	T
Polyphen		0.022	B
Vest4		0.099
MutPred		0.56		Loss of sheet (P = 0.0817)
MVP		0.58
MPC		0.056
ClinPred		0.084	T
GERP RS		1.3
Varity_R		0.013
gMVP		0.33
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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

hg19: chr10-124595702;