NM_022034.6:c.83-670A>G

Variant names:

• chr10-122841998-T-C
• rs2950366
• NM_022034.6:c.83-670A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022034.6(CUZD1):​c.83-670A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.443 in 151,678 control chromosomes in the GnomAD database, including 14,997 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.44 (14997 hom., cov: 31)
• Consequence: CUZD1 NM_022034.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.284
• Publications: 2 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.51 is higher than 0.05.

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.83-670A>G		intron	N/A	NP_071317.2
	CUZD1	NR_037912.2		n.97-2767A>G		intron	N/A
	FAM24B-CUZD1	NR_037915.1		n.759-670A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CUZD1	ENST00000392790.6	TSL:1 MANE Select	c.83-670A>G		intron	N/A	ENSP00000376540.1
	CUZD1	ENST00000338948.3	TSL:1	n.82+3764A>G		intron	N/A	ENSP00000340905.4
	CUZD1	ENST00000368900.5	TSL:1	n.83-2767A>G		intron	N/A	ENSP00000357896.2

Frequencies

GnomAD3 genomes AF: 0.443 AC: 67109 AN: 151560 Hom.: 14990 Cov.: 31

Gnomad AFR AF: 0.427

Gnomad AMI AF: 0.308

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.463

Gnomad EAS AF: 0.472

Gnomad SAS AF: 0.526

Gnomad FIN AF: 0.357

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.447

Gnomad OTH AF: 0.455

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.443 AC: 67142 AN: 151678 Hom.: 14997 Cov.: 31 AF XY: 0.441 AC XY: 32708 AN XY: 74100

African (AFR) AF: 0.427 AC: 17624 AN: 41314

American (AMR) AF: 0.489 AC: 7441 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.463 AC: 1604 AN: 3462

East Asian (EAS) AF: 0.470 AC: 2424 AN: 5158

South Asian (SAS) AF: 0.527 AC: 2526 AN: 4792

European-Finnish (FIN) AF: 0.357 AC: 3757 AN: 10516

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.447 AC: 30371 AN: 67898

Other (OTH) AF: 0.457 AC: 963 AN: 2106

Alfa AF: 0.449 Hom.: 1946

Bravo AF: 0.453

Asia WGS AF: 0.504 AC: 1754 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	14
DANN	Benign	0.94
PhyloP100		0.28
Mutation Taster		=100/0	polymorphism (auto)

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: rs2950366; hg19: chr10-124601514;