chr10-122834897-C-T

Variant names:

• chr10-122834897-C-T
• rs1322786665
• NM_022034.6:c.1191G>A

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.1191G>A​(p.Met397Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,216 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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: 0.0000062 (0 hom.)
• Consequence: CUZD1 NM_022034.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.146
• 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=0.20657533).

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.1191G>A	p.Met397Ile	missense	Exon 7 of 9	NP_071317.2
	CUZD1	NR_037912.2		n.1054G>A		non_coding_transcript_exon	Exon 6 of 8
	FAM24B-CUZD1	NR_037915.1		n.1867G>A		non_coding_transcript_exon	Exon 9 of 11

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CUZD1	ENST00000392790.6	TSL:1 MANE Select	c.1191G>A	p.Met397Ile	missense	Exon 7 of 9	ENSP00000376540.1	Q86UP6-1
	CUZD1	ENST00000338948.3	TSL:1	n.*139G>A		non_coding_transcript_exon	Exon 2 of 4	ENSP00000340905.4	A0A0A0MRA6
	CUZD1	ENST00000368899.5	TSL:1	n.1304G>A		non_coding_transcript_exon	Exon 4 of 6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250782 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000882

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000616 AC: 9 AN: 1461216 Hom.: 0 Cov.: 32 AF XY: 0.00000963 AC XY: 7 AN XY: 726896

African (AFR) AF: 0.00 AC: 0 AN: 33456

American (AMR) AF: 0.00 AC: 0 AN: 44678

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26114

East Asian (EAS) AF: 0.00 AC: 0 AN: 39672

South Asian (SAS) AF: 0.00 AC: 0 AN: 86186

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53386

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00000810 AC: 9 AN: 1111592

Other (OTH) AF: 0.00 AC: 0 AN: 60372

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000468 Hom.: 0

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions as Germline

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	Uncertain	0.46
BayesDel_addAF	Benign	-0.015	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	21
DANN	Benign	0.94
DEOGEN2	Benign	0.22	T
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.035
FATHMM_MKL	Benign	0.57	D
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.38	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.15
PROVEAN	Benign	0.51	N
REVEL	Uncertain	0.31
Sift	Benign	0.76	T
Sift4G	Uncertain	0.053	T
Polyphen		0.45	P
Vest4		0.39
MutPred		0.59		Gain of sheet (P = 0.0221)
MVP		0.62
MPC		0.27
ClinPred		0.63	D
GERP RS		3.9
Varity_R		0.17
gMVP		0.63
Mutation Taster		=87/13	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: rs1322786665; hg19: chr10-124594413;