10-122836358-GAAAAAAA-GAAAAA

Variant names:

• chr10-122836358-GAA-G
• rs11365591
• NM_022034.6:c.818-10_818-9delTT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_022034.6(CUZD1):​c.818-10_818-9delTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 1,095,246 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0025 (0 hom., cov: 0)
  • Exomes 𝑓: 0.20 (0 hom.)
• Consequence: CUZD1 NM_022034.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.127
• Publications: 1 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: Variant has high frequency in the AMR (0.247) population. However there is too low homozygotes in high coverage region: (expected more than 8623, got 0).
• BP6: Variant 10-122836358-GAA-G is Benign according to our data. Variant chr10-122836358-GAA-G is described in ClinVar as Benign. ClinVar VariationId is 402576.Status of the report is criteria_provided_single_submitter, 1 stars.

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.818-10_818-9delTT		intron	N/A	NP_071317.2
	CUZD1	NR_037912.2		n.681-10_681-9delTT		intron	N/A
	FAM24B-CUZD1	NR_037915.1		n.1494-10_1494-9delTT		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CUZD1	ENST00000392790.6	TSL:1 MANE Select	c.818-10_818-9delTT		intron	N/A	ENSP00000376540.1	Q86UP6-1
	CUZD1	ENST00000338948.3	TSL:1	n.83-1263_83-1262delTT		intron	N/A	ENSP00000340905.4	A0A0A0MRA6
	CUZD1	ENST00000368899.5	TSL:1	n.931-10_931-9delTT		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00246 AC: 346 AN: 140904 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00123

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00247

Gnomad ASJ AF: 0.00328

Gnomad EAS AF: 0.00144

Gnomad SAS AF: 0.00113

Gnomad FIN AF: 0.00979

Gnomad MID AF: 0.00336

Gnomad NFE AF: 0.00236

Gnomad OTH AF: 0.00470

GnomAD2 exomes AF: 0.296 AC: 21034 AN: 71052 AF XY: 0.293

Gnomad AFR exome AF: 0.300

Gnomad AMR exome AF: 0.293

Gnomad ASJ exome AF: 0.284

Gnomad EAS exome AF: 0.273

Gnomad FIN exome AF: 0.285

Gnomad NFE exome AF: 0.308

Gnomad OTH exome AF: 0.289

GnomAD4 exome AF: 0.203 AC: 194023 AN: 954342 Hom.: 0 AF XY: 0.206 AC XY: 96276 AN XY: 468494

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.206 AC: 4066 AN: 19764

American (AMR) AF: 0.254 AC: 3819 AN: 15030

Ashkenazi Jewish (ASJ) AF: 0.232 AC: 3457 AN: 14910

East Asian (EAS) AF: 0.252 AC: 6226 AN: 24738

South Asian (SAS) AF: 0.209 AC: 9336 AN: 44586

European-Finnish (FIN) AF: 0.249 AC: 7373 AN: 29638

Middle Eastern (MID) AF: 0.218 AC: 714 AN: 3280

European-Non Finnish (NFE) AF: 0.198 AC: 150702 AN: 762966

Other (OTH) AF: 0.211 AC: 8330 AN: 39430

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00249 AC: 351 AN: 140904 Hom.: 0 Cov.: 0 AF XY: 0.00324 AC XY: 220 AN XY: 67952

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00131 AC: 50 AN: 38300

American (AMR) AF: 0.00246 AC: 35 AN: 14212

Ashkenazi Jewish (ASJ) AF: 0.00328 AC: 11 AN: 3352

East Asian (EAS) AF: 0.00144 AC: 7 AN: 4850

South Asian (SAS) AF: 0.00137 AC: 6 AN: 4388

European-Finnish (FIN) AF: 0.00979 AC: 78 AN: 7966

Middle Eastern (MID) AF: 0.00368 AC: 1 AN: 272

European-Non Finnish (NFE) AF: 0.00236 AC: 153 AN: 64744

Other (OTH) AF: 0.00520 AC: 10 AN: 1924

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.13
Mutation Taster		=100/0	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: rs11365591; hg19: chr10-124595874;